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A Charge Equilibration Formalism for Treating Charge
Transfer Effects in MD Simulations: Application to
Water Clusters
Sudipta Kumar Sinha,[a,b] Mohit Mehta,[a] and Sandeep Patel
Conventional classical force fields by construction do not explicitly
partition intermolecular interactions to include polarization and
charge transfer effects, whereas fully quantum mechanical treat-
ments allow a means to effect this dissection (although not
uniquely due to the lack of a charge transfer operator). Considering
the importance of polarization in a variety of systems, a particular
class of classical models, charge equilibration models, have been
extensively developed to study those systems; since these types of
interaction models are inherently based on movement of charge
throughout a system, they are natural platform for including polar-
ization and charge transfer effects within the context of molecular
simulations. Here, we present two bond-space charge equilibration
models we term as QE2 and mixed QE2 treat charge transfer in
classical molecular mechanical calculations those provide practical
solutions to two major drawbacks of charge equilibration models:
(a) a nonvanishing amount of charge transfer between two heter-
oatoms at large separations, and (b) superlinear polarizability
Introduction
Classical force field-based molecular modeling is applied today
to a wide spectrum of physicochemical systems with the
aim of fundamental understanding of relevant attendant
processes.[1–6] By necessity, classical force fields only consider
fixed atomic charges and ignore quantum effects such as
polarization and its extreme form, which may be considered as
charge transfer in the molecular system. However, it is physi-
cally more realistic to assign charges based on the electron
density, which depend on their environment in a molecular
system. Results of studies based on ab initio and density func-
tional theory from the past decade have begun to point to
the significance of charge transfer effects related to a broad
class of physical, chemical, and biological systems.[7–14] Roux,
Klein, and their coworkers have demonstrated the nontrivial
effects of charge transfer in the selectivity filter of the KcsA
potassium-selective ion channel.[7,8] Liu, Head-Gordon, and
their coworkers showed the importance of charge transfer in
the hydrogen-bonded systems.[9,10] Charge transfer effects are
also important in terms of treating metalloenzymes in light of
the importance of such physiological moieties in human cellu-
lar function.[11,12] However, it is highly challenging to study
such systems using pure quantum mechanical or QM/MM
methods because the degrees of freedom of those systems
increase rapidly and they become computationally expensive.
The importance and incorporation of electronic polarization
effects in molecular simulations is becoming more widespread.
*[a]
scaling during bond dissociation due to charge transfer over
unphysical, large distances. To control charge transfer during disso-
ciation of a bond in a molecular system, we introduce a distance-
dependent scaling function (QE2 model) which, controls and
recovers physical behavior of the homonuclear and heteronuclear
charge transfer between two atoms at small and large values of
internuclear separation; and the mixed QE2 model in which we
combine the QE2 model under allow and disallow charge transfer
situations that describe both charge transfer and polarizability in a
distance-dependent manner. We demonstrate the utility of both
models in the case of a water dimer, and compare the results with
other existing models, and further, we perform short molecular
dynamics simulations for few water clusters with the QE2 model to
show the charge transfer and internuclear separation are correlat-
ed in dynamics. VC 2017 Wiley Periodicals, Inc.
DOI: 10.1002/jcc.24789
There are now several well-established classes of models that
effectively describe polarization effects in simulations. Major
approaches include (but in theory are not restricted to): induc-
ible dipoles, in which a set of additional variables are intro-
duced into the model to describe the dipole moment induced
by mutual polarization interaction[15,16]; Drude oscillator, where
polarization effects are considered based on the change in
separation between an atomic nucleus and an affixed charge
(Drude particle) coupled via a harmonic potential[17,18]; fluctu-
ating charge model, where polarization effect is described by
the charge distribution in response to the changes in geome-
try or external perturbations[19–21]; empirical valance bond
method, which parameterize the energy contributions of indi-
vidual valance bond configurations[22–24]; and effective frag-
ment potential, that uses energy decomposition of ab initio
[a] S. Kumar Sinha, M. Mehta, S. Patel
Department of Chemistry and Biochemistry, University of Delaware,
Newark, Delaware, 19716
E-mail: sapatel@udel.edu
[b] S. Kumar Sinha
Department of Chemistry, Indian Institute of Technology Ropar, Ropar,
140001, India
Contract grant sponsor: National Science Foundation; Contract grant
number: CAREER:MCB:1149802; Contract grant sponsor: National
Institutes of Health; Contract grant number: COBRE:P20-RR015588
(Chemical Engineering Department) and COBRE:P20-RR017716
(Department of Chemistry and Biochemistry at the University of
Delaware)
C 2017 Wiley Periodicals, Inc.
V
Journal of Computational Chemistry 2017, 38, 1389–1409 1389
 FULL PAPER WWW.C-CHEM.ORG
data to construct the parameterized effective potentials,[25,26]
among many others. Among these, the charge equilibration
model is a promising approach for the efficient inclusion of
explicit molecular polarizability and for allowing explicit treat-
ment of dynamics charge transfer.
In short, charge equilibration models typically redistribute
charges within a molecular system in an effort to model the
polarization response due to the conformational and environ-
mental changes. The partial charges on each of the atoms of a
molecule are found by minimizing the electrostatic energy
function subject to a constraint that the total charge of the
system is conserved. There are excellent parameterization
schemes available for this model in the literature.[27–30]
Because polarization is modeled by a redistribution of charge
over a predefined (although not necessarily unique) spatial
extent, the approach suffer from potential superlinear scaling
of polarizability with molecular size, an artifact requiring strict
attention when developing/parameterizing such models. This
is not to say that these models are ineffective. Polarizability
scaling behaviors have been addressed in several ways. Chelli
et al.[31] proposed an atom–atom or bond charge transfer
model, in an effort to eliminate this superlinear scaling of the
polarizability through topological control of charge transfer.
Shimizu et al.[32] proposed a constrained charge approximation
method, which consists of partitioning of the molecule into
multiple subsystems, where the net charge of a subsystem is
constrained to a fixed value and the transfer of charges among
them are not allowed. But this method is limited, because the
arbitrary partitioning of a molecule into such subsystems
offers no specific guidance into how these units should be
constructed, particularly if one is concerned about preserving
transferability. Nistor et al. introduced the split charge method,
which is a generalization of charge equilibration method for
nonmetallic materials.[33] Smirnov et al.[34] showed that the
split charge model yields correct electrostatic properties at rel-
atively weak perturbations. Warren et al.[33] discussed the ori-
gin and control of superlinear scaling of the polarizability in
the electronegativity equalization method. Despite the physi-
cality of charge transfer effects in condensed phase molecular
systems, due to the challenging nature of developing such
models, little work has advanced in this particular area of clas-
sical molecular modeling of force fields. In a recent work, Son-
iat et al.[35] showed the importance of polarization and charge
transfer in aqueous solution of ions.
Despite significant advances in development and applica-
tion, charge equilibration models formulated in bond-charge
representation suffers from unphysical charge distributions
predicted for geometries far from equilibrium. For example,
charge transfer over nonphysical atomic separations, or asym-
metric charge separation on salt dissociation. Chen et al.[21,36]
address this by introducing a distance dependent bond elec-
tronegativity into the model. They point out that the electro-
negativity should depend on the geometry of the molecule.
However, their model resolves the issue of unusual charge dis-
tribution at asymptotic limit of distances only for diatomic sys-
tem, but it does not resolve the problem in general. Moreover,
1390 Journal of Computational Chemistry 2017, 38, 1389–1409
their model continues to incorrectly model polarizability scal-
ing with system size.
In this work, we propose a modified charge equilibration
model in bond space, which resolves the issue of unusual dis-
tribution of charge at asymptotic limit in a general manner.
Technically, we have introduced a scaling function into the
model that equalizes the electronegativity of the system. We
refer the model as QE2 charge equilibration model based on
bond charge variables. Although QE2 provides sufficient flexi-
bility to model general properties of water clusters, but it does
not capture the physical behavior of polarizability scaling for
systems that are far from equilibrium. Therefore, we propose
another model termed as mixed QE2. This model predicts a
more physical behavior of polarizability of the system versus
separation of molecules; variation of molecular polarizability
with varying intermolecular distance is effectively varied varia-
tion with changing system size in the charge equilibration
sense. We demonstrate polarizability for a water dimer system
in this study. However, the QE2 model is sufficient to describe
the dynamics of charge transfer for moderate equilibrium sys-
tem, since it captures the physical behavior of charge transfer.
Therefore, we bound our system and perform molecular
dynamics simulations on water molecular clusters using the
QE2 model.
In the following section (Theoretical background section),
we first review pertinent details of existing charge equilibra-
tion models, their drawbacks, and our proposed models. In
Computational details section, we describe computational
details for model parameterization and dynamics of the sys-
tems. In Results and discussion section, we critically analyze
each of the models in a systematic manner. Summary section
extends the discussion on the results obtained from molecular
dynamics simulation trajectories. We conclude in the last
section with a summary of our findings and considerations for
future work related to this type of model.
Theoretical Background
We briefly review charge equilibration (QEq) or electronegativi-
ty equalization (EE) principle as described by Mortier et al.[37]
and later by Rappe and Goddard.[38] In this method, partial
atomic charges at a specific molecular site are variable so as
to induce a larger or smaller dipole moment of a group of
charges in response to a local electric field. The distribution of
charges is calculated by minimizing an energy function which
takes the form
X N
1X N
1
EðQÞ5 vi Qi 1 Jij Qi Qj 5QT v1 QT JQ (1)
i51
2 i;j51
2
where, the singly indexed upper-case charge variable Qi repre-
sents one of N partial atomic charges; the parameters vi and
Jii are the electronegativity and hardness of an atom i, respec-
tively. The terms Jij represent screened Coulomb interactions
between atoms i and j that are often taken to be the molecu-
lar Coulomb integral over atomic Slater or Gaussian orbitals
located on the respective nuclei. In this formulation, the
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diagonal homogeneous atomic hardness terms Jii represents

the self-Coulomb repulsion or idempotential, evaluated at zero
internuclear separation. An additional charge conservation
constraint such as

X
N
Qi 50 (2)
i51

is applied, which guarantees the neutrality of the system. Mini-

mizing the above energy function [eq. (1)] with respect to
each of the partial atomic charges subject to the constraint
eq. (2), yields a system of N – 1 linear equations for the Q0i s,
which can be written in matrix form as
J0 Q52Dv0
Figure 1. Illustration of atom (qi) and bond (pi) charges in molecular sys-
tem. The solid and dash lines in the figure represent the active and inac-
tive bonds of the system. The figure shows that only four unique bond
charges are sufficient to describe the electrostatistics of the system. The
bond charges are ranked in ascending order according to the increasing
order of distances between the pair of atoms. [Color figure can be viewed
(3) at wileyonlinelibrary.com]

in which J0 is the charge constrained atomic hardness matrix

(hardness matrix including the charge conservation con-
straint) having elements J1j0 51 and Jij0 5Jij 2J1j for all i 6¼ 1. A
positive definite J0 ensures a local minimum of the energy,
eq. (1).
The above QEq model works well for chemically reasonable
structures near equilibrium.[38] A surmountable drawback
involves charge transfer over distances defined by the spatial
extent of atomic sites involved in a group over which charge
is conserved. Approaches to deal with this are discussed in the
literature.[28,29,31,33,39] This precludes use of this current model
formulation in situations where chemical reactions are involved
and bond formation and dissociation occur. To address this
behavior in appropriate situations (i.e., bond dissociation),
recent investigations have found it advantageous to work in a
bond space built on two-site variables, qji corresponding to
pairs of atoms (atom pair 5 bond). The definition of bonds in
this scheme is more general, and it considers the bonds as
connections between two atoms involved in charge transfer.
Numerous nomenclatures can be found in literature defining
such bonds.[21,28,29,31,33,36]
The atomic and bond charge representations of the QEq/EE
formalism may be connected by the use of the projection
X
Qi 5 qji (4)
j XN X N
where the sum runs over all atoms j for which charge transfer
to atom i is allowed/defined given that the bond charge varia-
bles (denoted by the lower-case variables qji) satisfy antisym-
metry relation qij 52qji and that qii 5 0. The projection and
antisymmetry condition are compactly written as
degrees of freedom of the system is N – 1 no matter whether
the problem is expressed in atomic charge or bond charge
space. A representative figure has been shown in the Figure 1
to explain such connections. This involves restricting charge
transfer topology a priori and we refer to this as the active
topology in this work. It is important to keep in mind that the
active topology approach by its nature affords flexibility in
defining the topological nature of charge transfer, which we
believe to be a strength of an approach of this type. Although
in this work we use a fixed (constant) topology matrix, more
sophisticated implementations in the future can allow for
dynamic construction of the active topology space based on
appropriate cutoff functions; this would be of practical use for
MD and MC simulations with on-the-fly updates of the active
topology space.
Introducing bond charges in the atomic QEq method [eqs.
(1) and (4)], which we will refer to as the QE scheme, yields
X N X N
1X N X N X N X N
EðqÞ5 vi qji 1 Jij qki q‘j : (6)
i51 j51
2 i51 j51 k51 ‘51
By exploiting the antisymmetry, this expression can be writ-
ten[21,28] in the form
1X N X N X N X N  
EðqÞ5 ðvj 2vi Þ qji 1 Jik 2Ji‘ 2Jjk 1Jj‘ qji q‘k
i51 j>i
2 i51 j>i k51 ‘>k
(7)
for which pairs of indices are subject to the summation con-
ventions j > i and ‘ > k. Explicitly, the above equation in bond
space is

Q5Cq (5) X
Nbond

EðpÞ5 ðvatom2 2vatom1 Þ pi

where C is the connectivity or topology matrix for the charge i51
bond  
transfer. The dimension of the matrix, C, is ðN21Þ3NðN21Þ=2, 1 NX X
bond N

1 Jatomi atomj 2Jatomi atomj 2Jatomi atomj 1Jatomi atomj pi pj

without any topological constraints (i.e., charge transfer 2 i51 j51 1 1 1 2 2 1 2 2

allowed between all atomic sites). However, such connectivity (8)

or topology matrix cannot be used for practical purpose, since
it is rank deficient. Further, the number of physically significant or

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X
Nbond
1 NX X
bond N bond unmodified energy function in bond space and introduced p0i s
EðpÞ5 Dvi pi 1 gij pi pj (9)
2 i51 j51 into eq. (9), thus, the modified energy function becomes
i51

  NX
bond
1 NX X
bond N bond

where, gij 5 Jatomi atomj 2Jatomi atomj 2Jatomi atomj 1Jatomi atomj ; Dvi 5 Eðp0 Þ5 Dvi s21 0
i pi 1 gij s21 21 0 0
i sj pi pj (14)
1 1 1 2 2 1 2 2
i51
2 i51 j51
ðvatom2 2vatom1 Þ,
the singly indexed lower-case variable, pi rep-
resents a bond charge between atom1 and atom2; the parame- The above equation is now our working equation for this
ter Nbond is the number of charge transfer variables (bond study; this equation is referred as the QE2 model in this manu-
charges) in the system; the other parameters such as v and J script. The lowest energy in an active topology is obtained by
have their usual meaning as described before. The parameter differentiating eq. (9) w.r.t bond charges and equating it to
Nbond is N – 1 under the topological constraints. zero, resulting in Nbond number of simulation equations that
The above QE model [eq. (9)] does not yet eliminate the can be written as
drawbacks mentioned before, but rather it describes exactly
the same model in a different notation. However, it is a good oE NXbond
0
starting point for the manipulation of this model because the 0 5Dvi 1 gij s21
j pj 50 (15)
opi j51
transformed variables allow us to introduce a distance-
dependent function, f ðrÞ that penalizes long range charge
The above set of linear equations can be written in a matrix
transfer. Martinez and coworkers suggested an approach intro-
form as
ducing a distance dependent decaying function affecting the
electronegativity and they named their model QTPIE. They P0 52SG21 Dv (16)
wisely chose a function having properties of an overlap inte-
gral between orbitals on the ith and jth atoms. Their modified where S is a diagonal square matrix whose diagonal elements
energy function is are either 1 or a value determined by sðrÞ, and the off-
diagonal elements are 0, and G is the square, symmetric bond
NX
bond
1 NX X
bond Nbond
hardness matrix. The elements of the G matrix are given by
EðpÞ5 Dvi pi fi ðrÞ1 gij pi pj (10)
i51
2 i51 j51 the corresponding elements of the Hessian matrix as

The spirit of this approach provides a means to treat molecu- o2 E

5gii (17)
lar systems with extension to include intermolecular charge op02
i
transfer. In this work, we introduce scaling factors on the bond
charge (pi) that controls the value of bond charges. The scal- and
ing factor takes the value 1 if the corresponding bond is intra-
molecular. However, it takes the value from a distance- o2 E
5gij (18)
dependent function, sðrÞ, if the corresponding bond is inter- op0i op0j
molecular. Therefore, the effective bond charges, p0i , will follow
The above equation guarantees that the intermolecular bond
a relation as shown below
charges vanish in the asymptotic limit rij 5jri 2rj j ! 1 and the
p0i 5si ðrÞpi (11) results are physically meaningful. We demonstrated the valida-
tion of this new equation for heteronuclear diatomic and
or water dimer systems. The results have been presented in the
Supporting Information (Fig. S2) and Figure 3. On rearranging
0
pi 5s21
i ðrÞpi (12) the matrix equation, we obtain

We choose the function sðrÞ as a parametrized Slater overlap SGS21 P0 52SDv (19)
integral of the form
 
or
logðbrÞ
sðrÞ5a 1:02erf pffiffiffi (13)
c 2 G0 P0 52SDv (20)

where a, b, c are free parameters of the system and r is the
separation between two atoms. The choice of parametrized
Slater overlap integral over the actual Slater overlap integral is
beneficial since the latter is computationally expensive. The
function sðrÞ is chosen after performing various tests; the
superposition between the actual and parametrized Slater
overlap integral is presented in Supporting Information (Fig.
S1). To rederive the energy function we started from the
Thus, G0 is the similarity transformed matrix of G. Therefore,
the modified energy function as proposed in QTPIE will be
useful but we need to transform the original bond space to
another bond space for a physically meaningful result.
Although, this approach offers a way to overcome the short-
comings of the original QE model, since we introduce the
inverse of a decreasing distance-dependent function into the
energy expression, the potential for instabilities arises.

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 WWW.C-CHEM.ORG
We turn to discussion of electrostatic properties resulting
from this formalism. The system dipole moment is expressed as:
XN
~
l5 ri Qi (21)
i51
The above equation can be written in bond space as
XN XN
~
l5 ri Cpi 5 Dri pi 5DrT P (22)
i51 i51
Therefore, one obtains the system dipole moment from the
displacement vector, Dr, and bond charge vector, P. To obtain
the expression for polarizability, we are first required to mea-
sure the response of dipole moment of the system due to an
external electric field ~
e. If we assume that the strength of the
field is sufficiently small so that nuclear configuration of
the system is unchanged under ~ e, then the polarizability, a of
the system in bond space will be
a5DrT SG21 Dr (23)
The detailed derivation of the polarizability expression [eq.
(23)] can be found elsewhere.[31,39] Since the polarizability of
the system is quadratically related with displacement vector,
Dr, it grows quadratically with the increase of internuclear sep-
aration, and in fact the value of polarizability will be infinite if
some of the elements in the displacement vector ðDrÞ increase
to 1. Moreover, the intermolecular separation in a bulk molec-
ular system may be large but that does not necessarily mean
that the polarizability of the system will be large. As Bauer
et al.[40] showed the polarizability of a system of two water
molecules, at large intermolecular separation tends to the sum
of the individual water polarizabilities (on a per water mole-
cule basis). ab initio calculations also show that the total polar-
izability of a water dimer system is twice the value of the
individual isolated molecule polarizabilities. However, such a
problem is absent in dipole moment calculation, since it is lin-
early related with displacement vector, Dr. This is because the
bond charges vanish at asymptotic limit of the displacement
vector, and thus the product also vanishes at that limit. This
superlinear polarizability scaling has been discussed by Warren
et al.[39] and by Nistor et al.[33].
To address superlinear polarizability scaling, we devise a mixed
QE2 model. The model, in essence, is a linear combination of two
states, one allowing charge transfer, and the other suppressing
charge transfer over intermolecular separations. We next demon-
strate this model for a simple water dimer system which requires
only one intermolecular bond charge variable and captures
essential features of the model. The logic is extensible to a sys-
tem containing many molecules exchanging charge in pairwise
manner. The mixed QE2 model defines system polarizability as
a5haa 1ð12hÞad (24)
where aa and ad represent the two independent system polar-
izabilities under conditions of allowed and disallowed charge
FULL PAPER
transfer conditions. The element h is a mixing function, which
takes a value from another distance dependent function, hðrÞ
that smoothly varies from 0 to 1. However, it is convenient to use
h 5 0.5 for intramolecular bond charge variable and use a value
from the function hðrÞ for intermolecular bond charge variable. A
parameterized exponential type function, hðrÞ5expð2br 2 Þ, is
adopted here. We chose this function because the intermolecular
bond charges vanish almost exponentially with the increase of
intermolecular distances. Equation (24) allows us to deduce a
self-consistent representation for a modified bond charge vari-
able which is also of a linear combination form. This new bond
charge variable is given as (see Appendix for details).
p00i 5hpai 1ð12hÞd0 pdi (25)
where d0 takes a value either 0 or 1 depending on the type of
charge transfer (i.e., intermolecular or intramolecular).
Substituting the new bond charge variable into eq. (14), we
can define the new energy expression for mixed QE2 model as
X
Nbond
1 NX X
bond N bond
Eðp00 Þ5 Dvi s21 00
i pi 1 gij s21 21 00 00
i sj pi pj (26)
2 i51 j5i
i51
Details of this model are described in Appendix. The model is
useful to perform MD simulation for large molecular system in
a pairwise manner.
Computational Details
We first discuss estimation of model parameters for the water
cluster systems. The models possess atomic hardness (i.e.,
diagonal Jii elements), electronegativity (vi), and three parame-
ters of the function, sðrÞ, namely a, b, and c. For computational
simplicity, we consider the Jij, which is often known as hetero-
geneous hardness, and they are evaluated from the atom type
values based on the combining rule[41]
1
2 ðJii 1Jjj Þ
Jij ðrij ; Jii ; Jjj Þ5 qffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi
ffi (27)
11 14 ðJii 1Jjj Þ2 rij2
We treat the intramolecular heterogeneous hardnesses as
parameters in this study. A set of water clusters for this study
is taken from the Cambridge Cluster Database.[42] We first per-
form single point energy calculation on those water clusters in
gas phase at the mp2/aug-cc-pvdz level of theory using Gauss-
ian09 program.[43] The atomic charges of the systems are
determined by using CHELPG scheme from the current elec-
tron density at that level of theory. Once we obtain QM
charges, we calculate the difference of QE charges from them
and construct a cost function, Fcost, that contains all of the
above mentioned free parameters
XN
Fcost 5 ðDei Þ2 (28)
i51
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where Dei 5eQM QE

i 2ei ; and ei
QM
and eQE
i are atomic charges of Lennard–Jones (LJ) and intramolecular energy, and (b) QE
the system as computed using QM and QE methods; and eQE i molecular energy where the electrostatic energy is modified.
is a function of all the parameters of the system, which is giv- Additionally, a spherical harmonic boundary potential is
en by the following equation. applied to limit intermolecular separation distances. Explicitly,
the potential energy function, Uðp0 ; rÞ takes the following form
eQE 5CP0 52CSG21 Dv (29) "
XXX    #
0 rab 12 rab 6
where C is the connectivity or topology matrix for charge Uðp ; rÞ5 4Eab 2
j<i a b
ria;jb ria;jb
transfer. In the following step, we optimize the above cost
function w.r.t. each of the parameters of the system. To per- 1XXX  
2
1 Kb riab 2riab 1
form this optimization a Monte Carlo simulated annealing 2 i a b
(MCSA) method is applied to the system.[44] The MCSA is an
1XX NXbond
1 NX X
bond Nbond
iterative algorithm; we start with initial values of guess param- KE ðria 2rc Þ2 1 Dvi s21 0
i pi 1 gij s21 0 21 0
i pi sj pj
2 i a 2 i51 j5i
eter, a starting step vector whose dimension is identical to the i51

parameter vector, and a starting temperature. The initial values (30)

of the guess parameters are taken from the literature[45]; the
components of the starting step vector were set to a value of where r and E are LJ parameters; Kb and KE are bonded and

2.0; and the initial temperature was set to a value 1000 K. Dur- wall potential force constants, respectively; rab is the equilibri-
ing optimization, the MCSA algorithm generates a succession um bond length and rc is the boundary cutoff from the center
of parameters, that is, Monte Carlo (MC) moves, tending to of mass of the systems; J and v are the hardnesses and elec-
global minimum of the Fcost. New set of parameters are gener- tronegativities of the atoms. Bond charges and atomic posi-
ated around the current set of parameters by applying random tions are treated as independent dynamical variables. The total
moves along each coordinate direction, in turn. The new energy (i.e., Hamiltonian of the system) will be
parameter values are uniformly distributed in an interval cen- NX X
molec N atom
1 NXbond
1 :
tered around the current parameters. The width of the interval Hðp0 ; rÞ5 mia ria : 21 Mi p0i 21Uðp0 ; rÞ (31)
was chosen 610% of the current values of the parameter. Half i51 a51
2 i51
2
the size of these intervals along each direction is recorded in
step vector. The aim of the variation in step vector is to main- where ma is the atomic mass of atom a and Mi is the mass of
time2
tain the average percentage of accepted MC moves at about fictitious bond charge, p0i , with dimensions of energy 3 charge 2.

one-half of the total number of MC moves. If the point falls
outside the definition domain of Fcost, a new set of parameter
is randomly generated until a point belonging to the defini-
tion domain is found. A candidate set of parameter is accept-
ed or rejected according to Metropolis criterion[44] and the
process is continuing until a thermal equilibrium is reached.
After thermal equilibrium, the temperature of the system is
reduced at a rate of 0.95 and a new sequence of moves is
made starting from current set of optimized parameters, until
thermal equilibrium is reached again, and so on. The process
is terminated at a temperature low enough that no more use-
ful improvement of Fcost can be expected. The details of the
MCSA method can be found elsewhere.[44] Note that we sepa-
rately parameterized the Gaussian function h(r) for the mixed
QE2 model for water dimer using optimized parameters
obtained from the QE2 model. Since, we compare to existing
methods for treating intermolecular charge transfer, parame-
ters for a QTPIE-like model for the water cluster systems are
also computed by the above method. But instead of using the
complicated overlap integral, we use the the function s(r) for
computing the bond electronegativity for this model.
Once we obtain the parameters for the QE2 model, we per-
form molecular dynamics simulation on each of the water clus-
ters in gas phase (using only the QE2 model). To perform the
dynamics of the system, we define the potential energy func-
tion of the molecular system. The molecular potential energy
function of Nmolec system with Ni atoms of molecule i and
Nbond bond charge variables consists of two parts, (a)
Additional constraints on the bond charges are implicitly
included in the potential energy function described by eq. (3).
The nuclear degrees of freedom evolve according to Newton’s
equation
:: oUðp0 ; rÞ
ma ria 52 (32)
oria
and the set of bond charges evolve in time according to
:: oUðp0 ; rÞ
Mi p0i 52 (33)
op0i
The coupled equation of motion are numerically solved using
velocity-Verlet integrator. The detail set of parameters for these
simulations are presented in Table 1. The LJ parameters r and
E for oxygen were set to 2.50 Å and 0.2862 kcal/mol and the
corresponding values for hydrogen were set to 0.0 Å and 0.0
kcal/mol. The initial configuration of the systems consists of 3-
site water clusters containing Mwat water molecules, where the
values of Mwat vary from 2 to 5. We use the global optimized
QE parameters for the dynamics of each of the water clusters.
The mass of a bond charge, Mi is a fictitious quantity, chosen
to be small enough to guarantee that charges readjust rapidly
to changes in the nuclear degrees of freedom. The two force
constants Kb and KE are set to 53106 and 53105 kcal/mol,
respectively. We are required to use such high values of force
constants for each bond of the water molecules because we
do not apply any additional holonomic constraint force on

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Table 1. The global optimized parameters for OAO and OAH charge transfer as obtained from simulated annealing method are presented in the table.
Hardness (J)
(kcal/(mol e2))
Atomic Bond
Type O H OAH
OAO 334.56 388.27 257.77
OAH 335.95 388.28 257.81
The parameters for mixed QE2 model are also tabulated.
them; we thus acknowledge that we do not model true rigid
water models, but for the current purpose to demonstrate the
feasibility of models such as QE2 for molecular dynamics simu-
lations, we employ basic models. We further stress that since
we use an in-house MATLAB program to implement dynamics
using the QE2 models, we do not incorporate holonomic con-
straint algorithms from scratch as we feel these are not essen-
tial to our discussion. We first minimized total energy for each
of the cluster systems using steepest descent method. Then,
we performed molecular dynamics simulation in gas phase
using those minimized coordinates and bond charges of the
system. The systems are equilibrated for about 50 ps at con-
stant energy and then the simulations are continued at con-
stant temperature. The initial velocities of the nuclei and bond
charges are picked as Gaussian random numbers from Max-
well–Boltzmann distribution at 300 K and 5 K. Both nuclear
and bond charge degrees of freedom are coupled with veloci-
ty rescaling thermostat at those two temperatures during sim-
ulation. We have chosen 5:031022 fs time step for doing all of
these simulations.
All the simulations, optimizations, and the analyses of the
trajectories have been performed using our in-house MATLAB
(version:R2013)[46] code. We consider the two intramolecular
physical bonds of water molecules and Mwat 21 intermolecular
connections as bond charge variables. The network of Mwat 21
intermolecular connections is decided by considering the mini-
mum spacing between the center of mass of two water mole-
cules. Specifically, we determine the first pair of water
molecules that corresponds to the minimum value of intermo-
lecular distance of the system. We take this pair of water mole-
cules to correspond to the first connection of the network.
The next connection is decided by calculating the minimum
distance between a water molecule, which is outside of the
network, and the two terminal molecules of the existing net-
work. The process is continued until it reaches value of total
number of water molecules of the system.
We parameterized the systems and performed dynamics by
allowing both OAO and OAH intermolecular charge transfer.
We allow such type of charge transfer by changing only the
topology matrix of the system. We do not change the topolo-
gy matrix dynamically throughout our calculation in this study,
although, this is a feature to explore in the future. The visual
molecular dynamics (VMD) package[47] was used to monitor
the simulation, visualization, and graphics preparation for this
work.
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v
(kcal/(mol e))
b b
HAH O H a (Å21) c (Å22)
183.32 75.27 0.00 0.816 0.532 0.478 0.011
183.25 75.20 0.00 0.767 0.567 0.471 0.051
Results and Discussion
In this section, we present and discuss the results of our calcu-
lations for the models as outlined above. We start with discus-
sion of the critical aspects of the new model, its applicability,
and its validation. Finally, we discuss the results obtained from
MD trajectories for different sizes of water clusters in gas
phase.
Model validation
We first parameterize models using the water dimer system.
We treat cases for intermolecular charge transfer between (a)
two oxygen atoms on different molecules and (b) the oxygen
on water molecule and a single hydrogen atom on the second
water molecule. Parameters determined using the simulated
annealing methodology described earlier are used to compute
electrostatic properties of the system as a function of inter-
atomic separation, rij, where ij5OOorOH. The set of parameters
we obtain are presented in Table 1. The configuration of the
systems at different values of rij are generated by translating
one of the water molecules of the dimer along the OAH bond
vector formed between two water molecules. We illustrate the
process of such translation in Figure 2. We calculate the elec-
trostatic properties of water dimer for QE2 and mixed QE2
charge transfer models. We consider the two different scenari-
os of allowing intermolecular charge transfer and disallowing
intermolecular charge transfer for calculating the electrostatic
properties using the QE2 model. We further consider the
charge transfer between two water molecules happens
through (a) homonuclear (OAO), or (b) heteronuclear (OAH)
bond charge variables. In Figure 3, we illustrate the behavior
of electrostatic properties of the system as a function of rij. For
Figure 2. The process of translation of first water molecule in dimer has
been illustrated here. The first water molecule is translated along the vec-
tor formed between the oxygen of second water and the hydrogen of first
water, which is oriented to the oxygen of first water. [Color figure can be
viewed at wileyonlinelibrary.com]
Journal of Computational Chemistry 2017, 38, 1389–1409 1395
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Figure 3. The electrostatic properties of water dimer system as obtained from different QE and QTPIE models, and QM calculation. The four panels in the
figure describe the electrostatic energy (panel A), interwater bond charge (panel B), dipole moment (panel C), and polarizability (panel D) of the system as
a function of intermolecular distance. The solid and dash lines represent intermolecular OAO and OAH charge transfer, respectively. Smooth transition in
electrostatic properties with intermolecular separation between allow and disallow scenarios of QE2 model as obtained from mixed QE2 model is shown in
the insets. [Color figure can be viewed at wileyonlinelibrary.com]

comparison, we include results obtained from the QTPIE and
QM calculations.
Figure 3A describes the binding electrostatic energy
between two water molecules as a function of intermolecular
separations, DE(r), for all models discussed. The function, DE(r)
for a model is calculated by taking the difference in electro-
static energy between water dimer and two isolated water
molecules. We compare the results as obtained from different
charge transfer models and QM calculation in the figure. We
find the results obtained from all of the models and QM calcu-
lation are similar in nature. The function, DE(r) for the allowing
of OAO intermolecular charge transfer is identical for both
QE2 and QTPIE models. This is because the distance depen-
dent scaling function, s(r), for the allowing of OAO intermolec-
ular charge transfer in QTPIE model does not affect the
elements of bond electronegativity vector (Dv) and the bond
hardness matrix (G). Conversely, the function, s(r) acts twice in
the calculation of DE(r) in QE2 model; first it multiplies directly
for the calculation of effective bond charges (pis) and in the
following step, it multiplies inversely for the calculation of
energy of the system. Therefore, the effect of function, s(r)
cancels out from the energy calculation for this case. However,
the identical values of energy for both models is true for the
system containing one intermolecular bond charge variable
but such fact does not follow in a general manner for the sys-
tems having more than one intermolecular bond charge
variables. A significant difference in DE(r) function has been
found between QTPIE and QE2 models for the allowing of
OAH intermolecular charge transfer. This is not surprising
because the elements of bond electronegativity vector (Dv)
and bond hardness matrix (G) for the intermolecular bond
charge variables for QTPIE model vanish with the increase of
the distances between two water molecules, and the corre-
sponding intramolecular elements of the vector and matrix are
constants. Therefore, the values of intermolecular bond charge
for this model never vanish with the increase of distances
between two water molecules for the allowing of OAH inter-
molecular charge transfer. Thus, the function DE(r) as obtained
from this model for the allowing of homonuclear and hetero-
nuclear intermolecular charge transfer is significantly different.
Interestingly, our results show that the function DE(r) as com-
puted from the QE2 model for the allowing of homonuclear
and heteronuclear intermolecular charge transfer cases follows
similar behavior. This is because the function, s(r) controls the
elements of the Dv and G in such a way that the values of
intermolecular bond charge variables vanish at large values
of r. As a result the function, DE(r) is almost identical for the
cases of homonuclear or heteronuclear intermolecular charge
transfer. Moreover, slight difference in the values of parameters
for the allowing of OAO and OAH charge transfer are also
reflected in the DE(r) function at small values of r. Importantly,
the Gaussian function, h(r) that we introduce in the mixed QE2

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 WWW.C-CHEM.ORG
charge transfer model, transforms the energy function smooth-
ly from allow to disallow scenarios of QE2 model. Incorpora-
tion of the h(r) function into the model is necessary, which
ensures that the system behaves like water dimer at small val-
ues of r but it transforms to two isolated water molecules as
the values of r increase. We demonstrate such smooth transi-
tion between the two scenarios in the inset of Figure 3A.
Figure 3B, shows the magnitude of intermolecular bond
charge as a function of intermolecular separation, pi ðrÞ. We
calculate the function pi ðrÞ by allowing OAO or OAH charge
transfer between two water molecules present in the dimer.
Since there is no physical bond charge variable in QM calcula-
tion, we consider the difference in charge between the two
water molecules as bond charge variable for this case. The
function pi ðrÞ as obtained from the QE2, mixed QE2 models
and QM calculation is qualitatively similar. The magnitude of
intermolecular bond charge for the allowing of OAH charge
transfer is almost similar to the results obtained from QM cal-
culation. We show in the inset that pi ðrÞ as obtained from QE2
model for the allowing of either OAH or OAO intermolecular
charge transfer gradually vanishes with increasing the values
of r. We have also found that the function pi ðrÞ for OAO inter-
molecular bond charge transfer as obtained from the QE2
model is larger as compared to the result obtained from QM
calculation. Moreover, pi ðrÞ for intermolecular OAH bond
charge transfer as obtained from QTPIE model does not vanish
at large values of r. However, the introduction of s(r) into the
model nicely equalizes the electronegativity and hardness over
the system for QE2 model. The function pi ðrÞ as obtained from
mixed QE2 model transforms smoothly from allow to disallow
charge transfer scenarios of QE2 model as the values of r
increase, but such smooth transition is not prominent for the
dimer system, since the amount of charge transfer between
two water molecules is very small. We expect that such transi-
tion may be visible for efficient charge conducting materi-
als.[13,14] Additionally, we mapped the bond charges of the
system to atomic and molecular charges and the results are
presented in the Supporting Information (see Figs. S3 and S4).
So far we discuss that the QE2 model produces qualitatively
correct physical behavior of charge transfer for both homonu-
clear and heteronuclear intermolecular charge transfer cases.
Both QTPIE and the QE2 models redistribute atomic charges in
a different manner on each of the individual water molecules.
The distribution of atomic charges as calculated from QE2
model is also different for allow and disallow charge transfer
scenarios. The new distribution of atomic charge influences
the electrostatic properties such as dipole moment and polar-
izabilities of the system. Therefore, it is expected that the elec-
trostatic properties of the system is different at small and
large values of r. We calculated the magnitude of dipole
moment (l) and total isotropic polarizability (a) of the water
dimer system as a function of r. We consider the trace of diag-
onalized polarizability tensor as the isotropic polarizability of
the system. We presented the results in Figures 3C and 3D.
The net dipole moment vector of the system is computed
by adding all the individual bond dipole moment vectors of
the system. The result shows that the magnitude of dipole
FULL PAPER
moment of the system as obtained from the QE2 model varies
in a nonlinear and linear fashion at small and large values of r,
respectively. This is because the electrostatic field of each of
the water molecules influences each other at the small values
of r, but it gradually vanishes with the increase of the values
of r. The function lðrÞ as calculated by allowing OAO charge
transfer between two water molecules using QE2 model is
almost identical to the function as obtained by disallowing
charge transfer between them. This is because the value of
intermolecular OAO bond charge as calculated from the allow
scenario of QE2 charge transfer model is small at equilibrium
configuration of dimer, and it gradually vanishes with the
increase of distance between two water molecules. Therefore,
the dipole moment vector, which is associated to the intermo-
lecular bond charge variable of the system, vanishes quickly
with the increase of of the values of r. However, the magni-
tude of dipole moment for QE2 model as calculated by allow-
ing OAH intermolecular charge transfer is larger as compared
to the results obtained from OAO charge transfer. Since, the
value of intermolecular bond charge for intermolecular OAH
charge transfer is larger as compared to OAO charge transfer
at small values of r, the magnitude of net dipole moment vec-
tor for the former case is larger as compared to later one at
that region. Moreover, the magnitude of net dipole moment
for the allowing of either OAO or OAH charge transfer
reaches a constant value at large values of r, because, the
intermolecular bond dipole moment vector for both of the
cases vanishes with the increase of the values of r. The results
obtained from the mixed QE2 model for intermolecular OAO
and OAH charge transfer cases at small and large values of r
are similar with the results obtained from QE2 charge transfer
model under allow and disallow scenarios. The magnitude of
net dipole moment vector in QM calculation is computed by
adding the two dipole moment vectors of the individual mole-
cule present in the dimer of water. The magnitude of dipole
moment as obtained from QM calculation decreases at small
values of r, and it reaches to a constant value as the values of
r increases. The charge distribution of individual water mole-
cule at small values of r is quite different because the electro-
static field of each of the water molecules influences each
other at that region. We have found that the function lðrÞ as
obtained from QTPIE model for the allowing of either OAO or
OAH intermolecular charge transfer is significantly different.
Since the function pi ðrÞ for the allowing of OAO charge trans-
fer gradually vanishes with the increase of distance between
two water molecules, the magnitude of the corresponding
bond dipole moment vector also vanishes. Thus, the magni-
tude of dipole moment vector of the system as obtained from
this model is sum of the magnitude of individual dipole
moment vector of two water molecules at large values of r.
However, the magnitude of dipole moment as obtained from
this model for the allowing of heteronuclear intermolecular
charge transfer (OAH) increases linearly with the increase of
the values of r. Such a situation arises because of the presence
of a nonvanishing value of intermolecular bond charge vari-
able at large values of r for this case. The magnitude of dipole
moment vector associated with the nonvanishing bond charge
Journal of Computational Chemistry 2017, 38, 1389–1409 1397
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Figure 4. Representative snapshots of four water clusters obtained from MD trajectories. The top and bottom rows in the figure correspond the configura-
tions after equilibration and at the end of simulation. The intermolecular connections among water molecules for OAO intermolecular charge transfer are
represented by dashed line. The numbers in the figure correspond the intermolecular OAO distances between two water molecules in Å. [Color figure can
be viewed at wileyonlinelibrary.com]
variable causes increase the length of net dipole moment vec-
tor of the system.
Figure 3D describes the polarizability of the system as a
function of intermolecular separation, aðrÞ. The result shows
that the magnitude of polarizability of the system increases
with the increase of the values of r for both QTPIE and the
QE2 models. The result is inconsistent and shows the incor-
rectness of those models. However, the mixed QE2 model,
which we have demonstrated in this work, produces correct
behavior of the polarizability of the system at all values of r.
The magnitude of polarizability of the system as obtained
from mixed QE2 model is comparable with the results
obtained from QM calculation. This is an important finding
and enforces the applicability of the mixed QE2 model for
general molecular systems. However, the polarizabilities as
obtained from the QE2 charge transfer model are also reason-
able at small values of r; but the model over estimates the
polarizability with the increase of the values of r. Therefore,
the QE2 model is also equally applicable for the systems those
are not far from equilibrium. Importantly, the magnitude of
the polarizability of the system as obtained from QE2 charge
transfer model for the allowing of OAH intermolecular charge
transfer is larger as compared to the allowing of OAO charge
transfer between two water molecules. Such difference in
polarizability primarily arises because the magnitude of inter-
molecular bond charge variable of the system under those
two different charge transfer cases is significantly different.
However, the QTPIE model over estimates polarizability of the
system for the allowing of both OAO and OAH intermolecular
charge transfer cases.
Thus, it is clear from the above discussion that there are sig-
nificant drawbacks in QTPIE model and it raises questions on
the applicability of the model for general molecular systems.
1398 Journal of Computational Chemistry 2017, 38, 1389–1409
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We have shown in our study that the problem is severe, partic-
ularly for heteronuclear intermolecular charge transfer. Howev-
er, heteronuclear intermolecular charge transfer is common in
molecular system; and it fails to capture the correct physical
behavior of charge transfer in general. Conversely, the QE2
model reproduces correct behavior of charge transfer and rein-
forces the applicability of this model in the molecular system.
Additionally, we find that the QE2 charge transfer model does
not capture the correct physical behavior of polarizability of
the system at large values of r. Conversely, the mixed QE2
model reproduces qualitatively similar electrostatics as
obtained from QM calculation at all values of r. Since the QE2
model works well for the systems those are not far from equi-
librium, we use this model to study the dynamics of water
clusters in gas phase. In the following section we have
described that in detail.
MD trajectory analysis
In this section, we analyze the MD trajectories of each of the
water clusters. The initial and final configurations of each of
the clusters are presented in Figure 4. Since we have shown
before that the intermolecular bond charge as obtained from
QE2 model gradually vanishes with the increase of distances
between two water molecules, we are expecting a correlation
between bond charge variable and intermolecular separation
in the dynamics of those water clusters. We performed the
dynamics of the four water clusters by allowing either OAO or
OAH intermolecular charge transfer between two water mole-
cules present in the systems. Note that the length of the tra-
jectory for each of the water clusters is not equal because
such complex dynamics is computationally expensive for larger
clusters. We present scatter plots of intermolecular bond
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Figure 5. Correlation between intermolecular separation and the bond charges for OAO charge transfer. Four panels in the figure describe the results
obtained from the trajectory of water dimer, trimer, tetramer and pentamer. The reference zero line is included into the figure for differentiating sign of
the bond charges. Different color for each of the lines in the figure represents individual intermolecular connections. [Color figure can be viewed at
wileyonlinelibrary.com]

Figure 6. Correlation between intermolecular separation and the bond charges for OAH charge transfer. Four panels in the figure describe the results
obtained from the trajectory of water dimer, trimer, tetramer and pentamer. The reference zero line is included into the figure for differentiating sign of
the bond charges. Different color for each of the lines in the figure represents individual intermolecular connections. [Color figure can be viewed at
wileyonlinelibrary.com]

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Figure 7. Time evolution of intramolecular and intermolecular bond charges of water dimer, trimer, tetramer, and pentamer during OAO intermolecular
charge transfer. The left and right panels in the figure correspond the time evolution of intramolecular and intermolecular bond charges of the water clus-
ters. Unequal length of the trajectories have been marked by unequal tick space along the time axis. The color code of each of the lines represent different
bonds present in the system. [Color figure can be viewed at wileyonlinelibrary.com]

charges and their corresponding distances between two water
molecules in simulated clusters as obtained by MD with OAO
and OAH charge transfer separately in Figure 5 (for OAO
charge transfer) and 6 (for OAH charge transfer). We show
similar plots for results in larger clusters for each of the inter-
molecular bonds present in those clusters. We find that both
small and large clusters display similar correlation, and we
expect that such correlation may even hold in bulk systems.
The obtained results for the allowing of OAO or OAH inter-
molecular charge transfer follow almost similar type of correla-
tion. However, we find that the amount of charge transfer
under those two charge transfer situations is significantly dif-
ferent. Both of the figures show that the bond charge and the
distance between two water molecules are correlated for the
allowing of OAO and OAH charge transfer cases between
them. In particular, the correlation as obtained for dimer fol-
lows similar relationship as demonstrated in the previous sec-
tion. Therefore, the model that we propose in this work,
shows the correct behavior of charge transfer in the dynamics.
With increasing separation between the atoms of a bond
charge, there is a general decrease of charge transferred. The
profiles are not single-valued; this phenomenon arises from
the fact a particular bond charge variable represents the local
environment between two atoms. Since the local environment
around two atoms can be different, the same separation of
two atoms can be associated with nontrivial differences in the
amount of charge transferred between the two atoms. The
results as obtained from larger clusters by allowing OAO or
OAH intermolecular charge transfer in dynamics are consistent
with the calculated results as demonstrated before for the QE2
model. However, slight increase in the value of bond charge is
observed at small values of intermolecular separation for the
allowing of OAH charge transfer between two water mole-
cules for larger cluster. Such increase in the values of bond
charge may happen due to the several factors such as: (a) the
scaling function or parametrized overlap integral is not a per-
fect exponential function at small values of internuclear sepa-
ration, rather it is almost constant at that region of distances,
(b) the collective effect of all bond charge variables to the spe-
cific one, (c) equation of motions for charge dynamics are non-
linear in nature, and so forth.
In the next section, we discuss the dynamics of the bond
charges, atomic charges and the derived electrostatic proper-
ties such as dipole moment and polarizability of each of the
clusters. Finally, we discuss the time averaged properties of
water clusters those we obtain from the molecular charge

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Figure 8. Time evolution of intramolecular and intermolecular bond charges of water dimer, trimer, tetramer, and pentamer during OAH intermolecular
charge transfer. The left and right panels in the figure correspond the time evolution of intramolecular and intermolecular bond charges of the water clus-
ters. Unequal length of the trajectories have been marked by unequal tick space along the time axis. The color code of each of the curves represent differ-
ent bonds present in the system. [Color figure can be viewed at wileyonlinelibrary.com]

dynamics for each of the water clusters in the following
section.
Dynamical properties. In Figures 7 and 8, we show the time
evolution of intramolecular and intermolecular bond charge
variables as obtained by allowing OAO or OAH charge trans-
fer between two water molecules for four water clusters. The
left panels show the intramolecular bond charge transfer
(intramolecular bond charge transfer is charge transferred
between the bonded atoms in the actual molecule) and the
right panels show intermolecular bond charge transfer (charge
transferred between molecules along the allowed bond charge
variable; in the case of the dimer, there is only 1 bond charge
variable, in the case of the trimer, 2; in the case of the tetra-
mer, 3; and in the case of the pentamer, 4 bond charge varia-
bles). Shown are trajectories of individual bond charge
variables; only a single trajectory for each cluster has been
computed, and thus shown in these figures. In general both of
the intermolecular and intramolecular bond charge variables
are dynamic and fluctuate around an equilibrium value and
the fluctuation is similar for all the clusters. For instance, there
is a peak at about 3 ns for both intermolecular and intramo-
lecular bond charge of dimer. A positive peak for
intermolecular charge transfer suggests that the two water mol-
ecules are close to each other at that particular instant. As a
result the values of intramolecular bond charge decrease since
the whole system is neutral. Since the distance between two
water molecules present in the system changes during dynam-
ics, the amount of intramolecular and intermolecular bond
charge also follow that fact. Once again, we have seen from the
dynamics that the amount of transferred charge through OAH
intermolecular bond charge variable is larger as compared to
the OAO intermolecular bond charge variable. However, the
molecular charge dynamics under both charge transfer situa-
tions is almost similar for each of the water clusters.
The new distribution of bond charge influences the atomic
charges of each of the water molecules present in different
clusters. In Figures 9 and 10, we present the results as
obtained from four water clusters by the allowing of either
OAO or OAH intermolecular charge transfer. The figures show
that the atom and bond charges follow similar behavior in the
dynamics of the clusters. However, atomic charges are more
realistic than bond charges and give a clear understanding of
such charge dynamics for the water cluster systems.
The charge dynamics of individual water molecules is pre-
sented in Figures 11 and 12. The result shows that each of the

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Figure 9. Time evolution of oxygen (left panels) and hydrogen (right panels) atomic charges water clusters for OAO charge transfer. Unequal length of the
trajectories have been marked by unequal tick space along the time axis. The color code for each of the curves represent different atoms present in the
system. [Color figure can be viewed at wileyonlinelibrary.com]
water molecules possess a net charge and they are occasional-
ly neutral during dynamics, however, the sum of the charges
of individual water molecules at an instant is always zero.
Therefore, the neutrality of system is well maintained in the
dynamics, which is also shown in the figure. The variation of
water charges as a function of time for each of the clusters
are different, but they fluctuate around an equilibrium value.
Once again we see from the figure that the fluctuation of
water charge by allowing OAO and OAH intermolecular
charge transfer situations is similar. However, a water molecule
gains more charge if it transfers through OAH intermolecular
bond charge variable. Such result is also in agreement with
our previous analysis. Therefore, we expect that the QE2 mod-
el captures a realistic picture of charge dynamics for each of
the water cluster systems. We note that the initial charges on
individual water molecules may or may not be identically neu-
tral due to the fact that we start from classically optimized
geometries; at these configurations, some charge transfer is
allowed, and depending on the configuration, some molecules
may be neutral, while others not. In total, the systems are all
neutral during the entire trajectory as the total system charge
is constrained to be zero. Since the atomic and molecular
charges are dynamic, the electrostatic properties of the system
1402 Journal of Computational Chemistry 2017, 38, 1389–1409
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such as dipole moment and polarizability are also expected to
be dynamic. We computed the magnitude of dipole moment
and polarizability of each of the water clusters using the pro-
tocol as described in previous section (Theoretical background
section). We calculated those properties by the allowing of
either OAO or OAH intermolecular charge transfer in different
water clusters. The results are presented in Figures 13 and 14.
As we mentioned before, the magnitude of dipole moment of
the system depends on the length and orientation of each of
the bond dipole moment vectors present in the system. Since
both of the intermolecular separation and the bond charge
are dynamical variables, hence as a consequence, each of the
bond dipole moment vectors of the system is dynamic, which
is reflected in the figure. Moreover, the figure shows that the
magnitude of net dipole moment vector for each of the water
clusters is comparable in the short simulation. But the magni-
tude of dipole moment vector for the allowing of OAH inter-
molecular charge transfer is larger as compared to the
allowing of OAO intermolecular charge transfer. The polariz-
ability for each of the systems shows an interesting feature in
the dynamics. The figures show that the magnitude of polariz-
ability by allowing of either OAO or OAH intermolecular
charge transfer is quite different in dynamics. This is because
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Figure 10. Time evolution of oxygen (left panels) and hydrogen (right panels) atomic charges water clusters for OAH charge transfer. Unequal length of
the trajectories have been marked by unequal tick space along the time axis. The color code for each of the curves represent different atoms present in
the system. [Color figure can be viewed at wileyonlinelibrary.com]

the polarizability of the system is quadratically related with
the internuclear separations. Therefore, it indicates that the
nuclei dynamics for each of the systems may be quite different
under the two charge transfer situations. Moreover, the magni-
tude of polarizability increases with the increase of the size of
the cluster, which is again in agreement with our common
understanding.
Thus, it is clear from the above discussion that the molecu-
lar charge dynamics for the allowing of either OAO or OAH
charge transfer between two water molecules is quite similar.
However, the magnitude of transferred charge by allowing
OAH intermolecular charge transfer is larger as compared to
the results obtained by the allowing of OAO intermolecular
charge transfer. The neutrality of each of the systems is well
maintained during dynamics. Finally, the derived electrostatic
properties such a dipole moment and polarizability are consis-
tent with our proposed model in the dynamics.
Static properties. In this section, we further analyzed the MD
trajectories of water clusters as obtained by allowing either
OAO or OAH charge transfer between two molecules. Specifi-
cally, we calculated the distributions of intermolecular distance,
relative orientation between two water molecules, and charges
for each of the water clusters. The results are shown in Figures
15–17. It is clear from Figure 15 that there is an optimum sep-
aration between two water molecules in the dynamics of
water cluster systems. We observed that such results are true
for both OAO and OAH intermolecular charge transfer cases.
We define the relative orientation between two water mole-
cules as the angle between two dipole moment vectors of
them. The distribution of relative orientation between a pair of
water molecule is shown in Figure 16. The results have an
interesting feature, we observed that there is a preferential ori-
entation between the two water molecules those are engaged
in charge transfer. The preference in orientation increased
from smaller to larger water clusters. We also observed from
the figure that the pattern of such distribution by allowing
OAO and OAH intermolecular charge transfer cases is similar.
Therefore, such geometrical preference, which is pretty com-
mon in the molecular systems, influences on the charge trans-
fer among the water molecules in the cluster systems (see Fig.
16). Once again we have seen from the dynamics that the
magnitude of transferred charge for the allowing of OAH
charge transfer between two water molecules is larger as com-
pared to the magnitude obtained by allowing OAO charge
transfer between them. The distance between two water

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Figure 11. Time evolution of water charges in water dimer, trimer, tetramer, and pentamer for allowing intermolecular OAO charge transfer. Different
length of the trajectory for each of the clusters has been depicted by unequal tick space along x-axis. The color codes of each curve represent different
water molecules present in the system. The neutrality line (orange) as shown in each panel is the sum of all the water charges at any instant. [Color figure
can be viewed at wileyonlinelibrary.com]

Figure 12. Time evolution of water charges in water dimer, trimer, tetramer, and pentamer for allowing intermolecular OAH charge transfer. Different
length of the trajectory for each of the clusters has been depicted by unequal tick space along x-axis. The color codes of each curve represent different
water molecules present in the system. The neutrality line (orange) as shown in each panel is the sum of all the water charges at any instant. [Color figure
can be viewed at wileyonlinelibrary.com]

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Figure 13. Time evolution of system dipole moment (left panels) and polarizability (right panels) of water dimer, trimer, tetramer, and pentamer during
OAO intermolecular charge transfer. Different length of the trajectory for each of the clusters has been depicted by unequal tick space along x-axis.

molecules and orientation of each of the water molecules
affect the magnitude of charge transfer. We show the time
average magnitude of transferred charge between two nearest
nalyser water molecules present in four clusters in Figure 15.
Once again we found optimum values of transferred charge,
which is correlated with intermolecular bond distance.
Thus, it is clear from the above discussion that there is a
geometrical preference for the allowing of charge transfer
among water molecules present in the clusters. An orientation-
al preference for the intermolecular charge transfer increases
from smaller to larger clusters. Such geometrical preference is
pretty common in chemical and biochemical systems. Thus,
our analyses reveal that the combination of the geometrical
preference and the magnitude of bond charge determine the
stability, hydrogen bonding preference, and other physico-
chemical properties of a chemical system. Therefore, we need
an extensive study on larger cluster systems and we are cur-
rently doing that in our laboratory.
Summary
In this work, we develop a general charge equilibration model
in bond charge space (QE) that exhibits correct behavior of
charge distribution for dissociative molecular systems. Our
new QE2 model is more general and applicable for both
homonuclear and heteronuclear charge transfer in molecular
system. To formulate the QE2 model, we introduce a distance
dependent scaling function into the original QE model, which
ensures that the charge transfer variables vanish asymptoti-
cally with distances. The model works perfectly for systems
those are not far from equilibrium configuration. Moreover,
we show that only distance dependent pairwise electronega-
tivity into the model does not solve the issue of unusual dis-
tribution of atomic charges over large distances in a general
manner.
We first obtain the parameters of the system using simulat-
ed annealing method. We chose a system of clusters contain-
ing 2, 3, 4, 5 water molecules in this study. Explicitly, we
minimize a cost function, which is the difference between two
charges as obtained from QM calculation and the QE2 model,
contains all the free parameters of the system. We consider all
of the water clusters together during the minimization. Once
we obtain the parameters of the system, we analyze the water
dimer system. In the following step, we couple the QE2 model
with molecular mechanics energy function, construct the Ham-
iltonian and perform dynamics of each of each of the water

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Figure 14. Time evolution of system dipole moment (left panels) and polarizability (right panels) of water dimer, trimer, tetramer, and pentamer during
OAH intermolecular charge transfer. Different length of the trajectory for each of the clusters has been depicted by unequal tick space along x-axis.

Figure 15. Distribution of intermolecular distances between two nearest neighbor water molecules present in four clusters. The analyses have been performed
using the MD trajectories as obtained for allowing OAO and OAH intermolecular charge transfer. [Color figure can be viewed at wileyonlinelibrary.com]

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 WWW.C-CHEM.ORG FULL PAPER

Figure 16. Distribution of angles between two dipole moment vectors of two nearest neighbor water molecules present in four clusters. The analyses
have been performed using the MD trajectories as obtained for allowing OAO and OAH intermolecular charge transfer. [Color figure can be viewed at
wileyonlinelibrary.com]

clusters. Note that we perform all of our calculation using our
in-house MATLAB program.
First, we critically nalyse our model by translating one of the
water molecule present in water dimer. We show that our
model works perfectly at the asymptotic limit of distances. We
also validate that the model is applicable for both OAO and
OAH intermolecular charge transfers. However, we find that
the magnitude of intermolecular charge transfer for allowing
OAH intermolecular charge transfer is larger as compared to
the OAO charge transfer. Such result is quite reasonable, and

Figure 17. Time average magnitude of transferred charge between two nearest neighbor water molecules present in four clusters. The analyses have
been performed using the MD trajectories as obtained for allowing OAO and OAH intermolecular charge transfer. [Color figure can be viewed at
wileyonlinelibrary.com]

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 FULL PAPER WWW.C-CHEM.ORG
it is in agreement with our model because the large differences
in electronegativity and hardness between Oxygen and Hydro-
gen atoms drive such larger amount of charge transfer. Since the
atomic charges of the system change with intermolecular separa-
tion, it is expected that the electrostatic properties of the system
follow that fact. We compute both dipole moment and polariz-
ability of the dimer system as a function of distance between
two water molecules. Our analysis reveals that the model produ-
ces correct behavior of dipole moment of the system but it does
not capture the correct behavior of the polarizability of the sys-
tem at large values of intermolecular separation. However, the
model is reasonable to use for further study for a bound system.
Since the QE2 model is a reasonable choice for a bound sys-
tem, we use it to perform molecular dynamics simulation for
each of the water clusters within a sphere. We show a correlation
between intermolecular distances and bond charge variables
through the dynamics. Existence of such a correlation reinforces
the assessment of the QE2 model. Our results also reveal that the
new distribution of bond charge modifies the the atomic and
water charges of the system. We also show that the neutrality of
the system is well maintained during the dynamics. The new dis-
tribution of the charges affects the electrostatic properties such
as dipole moment and polarizability of the system. Importantly,
we find that the dynamics of charges and derived dipole
moment of the systems by allowing both OAO and OAH charge
transfers follow similar behavior. However, we find a significant
difference in dynamics of the polarizability of the systems
between the OAO and OAH intermolecular charge transfer.
Since the polarizability of the system is a function of bond hard-
ness matrix and molecular configurations, hence it may be
expected that the configurations and charges of the systems
under those two conditions are not identical. We analyze inter-
molecular separation, orientation, and the charge for each of the
trajectories of water cluster. Our analysis reveals that the configu-
rations of the system are similar under two charge transfer condi-
tions, but the intermolecular charges of the systems under those
two charge transfer conditions are significantly different.
We discuss that the QE2 model works well for chemically rea-
sonable structure but it overestimates the polarizability of the sys-
tem. To overcome this problem, we demonstrate another model,
which we refer to as mixed QE2 model. The model constructs a
new bond charge variable, which is a combination of two bond
charge variables of the system as obtained from QE2 model under
allow and disallow scenarios. A Gaussian function, which we intro-
duce in this model, combines those two bond charges. We dem-
onstrate the model and calculate the electrostatic properties of
water dimer system in this study. The mixed QE2 model over-
comes drawbacks of the QE2 model. However, we need a general
formulation of the model and need to apply it on a large molecu-
lar system. We are currently doing that in our laboratory.
Appendix
Mixed QE2 Model
polarizability of the system grows quadratically with the
increase of internuclear separation. Therefore, we wish to con-
trol such increase in polarizability of the system in a systematic
manner. However, the central issue in this problem is that the
dimension of the system in bond charge space is not identical
at short and large internuclear distances. Such situation is
pretty common in chemical reactions, where the formation
and breaking of the chemical bonds take place. Therefore, we
aim to remove the irrelevant bond charge variable from the
system in a systematic manner. We consider the net polariz-
ability of the system is a mixture of two polarizabilities of the
system under allow and disallow charge transfer conditions in
an appropriate proportion.
Consider a bimolecular system and there is only one intermo-
lecular bond charge variable then the polarizability tensor of
the system, a, can be defined as
a5haa 1ð12hÞad (A1)
where, h is the mixing function, which takes a value from a
distance dependent function, hðrÞ, where r is the intermolecu-
lar distance. It is clear from the equation that the contribution
of aa is dominating if the intermolecular charge transfer is
allowed. Conversely, ad is dominating if there is no intermolec-
ular charge transfer. Multiply electric field vector, ~
e, on both
sides of the above equation, we can obtain the induced dipole
moment, ~ l ind for each of the situations
~ l aind 1ð12hÞ~
l ind 5h~ l dind (A2)
l ind can be expressed in the following way.
The ~
DRT DP00 5DRaT HDPa 1DRdT ðI2HÞDDPd (A3)
where, DR and DP are the displacement and induced bond
charge vectors; the elements of diagonal matrix, H are either 0.5
or take a value from the hðrÞ function for intramolecular and
intermolecular charge transfer, respectively, and I is the identity
matrix. The above equation is general and applicable for multi-
molecular system. Since, the dimensions of both of the vectors,
DPa and DPd are not identical, a rectangular D matrix is intro-
duced into the equation. Since the configuration of the system
is unchanged under those three situations, hence
DRT 5DRaT 5DRdT (A4)
therefore,
DP00 5HDPa 1ðI2HÞDDPd (A5)
On rearrangement, we can obtain
   
P~e 00 2P00 5H P~ea 2Pa 1ðI2HÞD P~ed 2Pd (A6)
or
In this article, we introduce another new model, which we    
refer as mixed QE2 model [Eq. (26)]. As discuss before, the P~e 00 2P00 5 HP~ea 2ðI2HÞDP~ed 2 HPa 2ðI2HÞDPd (A7)

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where the ~e represents the external electric field. Comparing [11] D. V. Sakharov, C. Lim, J. Am. Chem. Soc. 2005, 127, 4921.
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1 NX X
bond Nbond

Eðp00 Þ5 Dvi s21 00

i pi 1 gij s21 21 00 00
i sj pi pj (A10)
i51
2 i51 j5i
According to this model, the value of bond charge is con-
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intermolecular separation increases.
Acknowledgment
SP thanks N. Patel for fruitful discussion and encouragement for the
duration of this work.
Keywords: charge transfer  charge equilibration  polariza-
tion  force field  molecular dynamics  simulation
How to cite this article: S. Kumar Sinha, M. Mehta, S. Patel. J.
Comput. Chem. 2017, 38, 1389–1409. DOI: 10.1002/jcc.24789
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Received: 1 September 2016
Revised: 16 January 2017
Accepted: 17 January 2017
Published online in Wiley Online Library

Journal of Computational Chemistry 2017, 38, 1389–1409 1409