Molecular Mechanics Methods

MS CHEMISTRY SPRING2023
Submitted to: Dr. Majid Gill
RIPHAH INTERNATIONAL UNIVERSITY
FAISALABAD
Group Members :

UMAIR AKRAM
MUHAMMAD KASHIF
QANDEEL ABDUL SAMAD
ALIYA ARSHAD
RABI TAHIR
MUHAMMAD REHAN
CONTENTS
 Computational Chemistry
 Tools of Computational Chemistry
 Molecular Mechanics
Advantages
Disadvantages
The Force Field
Vander Waals energy
Different force field Methods
Merck molecular force field
 AMBER • CHARMM • GROMOS • OPLS • CFF • COMPASS • MMFF
Computational Chemistry:
Computational chemistry is the branch of chemistry that
uses computer simulation to assist in solving chemical
problems. It uses methods of theoretical chemistry,
incorporated into computer programs, to calculate the
structures and properties of molecules, groups of molecules,
and solids.
Tools of Computational Chemistry:
Computational chemists have a selection of methods at their disposal.
The main tools available belong to five broad classes:
Molecular Mechanics
Ab initio calculations
Semi empirical methods
Density functional theory
Molecular dynamics
Molecular Mechanics :
Molecular mechanics is based on a model of a molecule as a collection of
balls (atoms) held together by springs (bonds).
By knowing the spring lengths, their angles and how much energy it takes
to stretch and bend the springs, we can calculate the energy of a given
collection of balls and springs, i.e., of a given molecule.
Geometry is changed until the lowest energy is found enables us to do a
geometry optimization.
Molecular mechanics is fast, a fairly large molecule a steroid (e.g.,
cholesterol C27H46O) can be optimized in seconds on a good personal
computer.
Molecular mechanics uses classical mechanics to model molecular
systems.
Molecular mechanics can be used to study molecule systems ranging in
size and complexity from small to large biological systems.
All-atomistic molecular mechanics methods have the following properties:
 Each atom is simulated as one particle.
 Each particle is assigned a radius (typically the Vander Waals radius),
polarizability, and a constant net charge (generally derived from quantum
calculations and/or experiment).
 Bonded interactions are treated as springs with an equilibrium distance
equal to the experimental or calculated bon length.
Advantages :
Molecular mechanics methods are less complicated,
fast, and are able to handle very large systems
including enzymes.
Molecular mechanics may give extremely accurate
energies if the proper parameters are available.
Disadvantages :
A disadvantage of molecular mechanics is that
parameters are derived for ground State systems and
are consequently unable to adequately represent
geometries in bond making and bond breaking
processes.
The Force-Field:
Molecular mechanics expresses the total energy as a
sum of Taylor series expansions for stretches for
every pair of bonded atoms, and adds additional
potential energy terms coming from bending,
torsional energy, van der Waals energy, electrostatics,
and cross terms
Vander Waals energy:
The van der Waals energy arises from the interactions
between electron clouds around two non-bonded atoms
• Short range: strongly repulsive
• Intermediate range: attractive
• Long range: goes to zero
The attraction is due to electron correlation which results in
“dispersion” or “London” forces (instantaneous multiple /
induced multiple).
Different Force Field Methods:
 Class I Methods:
Higher order terms and cross terms. Higher accuracy, used for small
or medium sized molecules. Examples: Allinger’s MM1-4, EFF, and
CFF.
 Class II Methods:
 For very large molecules (e.g., proteins). Made cheaper by using
only quadratic Taylor expansions and neglecting cross terms.
Examples: AMBER, CHARMM, GROMOS, etc. Made even cheaper
by using “united atoms.
Merck molecular force field:
Merck molecular force field (MMFF) is a family of
chemistry force fields developed by Merck research
laboratories
The parameters in the force field have been derived from
computational data consisting of approximately 2800
structures spanning a wide range of chemical classes.
The first published force field in the family is MMFF94.
AMBER: (Assisted model building and energy
refinement) :
• is a family of force fields for molecular dynamics of biomolecules.
• originally developed by peter Koolman's group at the university of California,
San Francisco.
• AMBER is also the name for the molecular dynamics software package that
simulates force fields.
• The AMBER force field is a widely used molecular mechanics force field in
computational chemistry and molecular modeling.
• It is used to describe the intermolecular interactions and energy calculations of
biomolecules such as proteins, nucleic acids, and carbohydrates.
• The AMBER force field is developed by fitting parameters to experimental data,
quantum mechanical calculations, or a combination of both.
• The parameterization is typically done for specific types of molecules, such as proteins
or nucleic acids, and may be further refined for particular chemical environments or
functional groups.
 Parameter sets:
• To use the AMBER force field, it is necessary to have values for the parameters
of the force field.
• Each parameter set has a name, and provides parameters for certain types of
molecules
• Peptide, protein, and nucleic acid parameters: parameter sets with names
beginning with "ff" and containing a two digit year number, for instance "ff99".
• General AMBER force field (GAFF) provides parameters for small organic
molecules to facilitate simulations of drugs and small molecule ligands in
conjunction with biomolecules.
• The GLYCAM force field : for carbohydrates.
As of 2018 the primary protein model used by the AMBER
suit is the ff14SB.
The primary force field used in the AMBER suit for lipids
is lipid1
Software:
The AMBER software suite provides a set of programs to apply the
AMBER force fields to simulations of biomolecules.
It is written in the programming languages Fortran 90 and C, with support
for most major Unix-like operating systems and compilers.
 Development is conducted by a loose association of mostly academic labs.
New versions are released usually in the spring of even numbered years;
AMBER 10 was released in April 2008.
 The software is available under a site license agreement, which includes
full source, currently priced at US$500 for noncommercial and US$20,000
for commercial organizations.
OPLS: (Optimized Potentials for Liquid
Simulations) :
The OPLS (Optimized Potentials for Liquid Simulations) force field was developed
by Prof. William L. Jorgensen at Purdue University and later at Yale University.
The OPLS (Optimized Potentials for Liquid Simulations) force field is a widely
used classical force field for molecular dynamics simulations in computational
chemistry and biochemistry. It is known for its accuracy in describing a wide range
of chemical systems, including organic molecules, proteins, and nucleic acids.
However, it's not clear what you mean by "Mothed."
Several sets of OPLS parameters have been published. There is OPLS-ua (united
atom), which includes hydrogen atoms next to carbon implicitly in the carbon
parameters, and can be used to save simulation time.
A distinctive feature of the OPLS parameters is that they were optimized to fit
experimental properties of liquids, such as density and heat of vaporization.
Implementation:
The reference implementations of the OPLS force field are
the BOSS and MCPRO programs developed by Jorgensen.
Other packages such as TINKER, GROMACS, PCMODEL,
Abalone, LAMMPS, Desmond and NAMD also implement
OPLS force field
CHARMM: (Chemistry at Harvard
Macromolecular Mechanics) :
 A molecular simulation program with broad application to many-particle systems with a
comprehensive set of energy functions, a variety of enhanced sampling methods, and
support for multi-scale techniques including QM/MM, MM/CG, and a range of implicit
solvent models.
 CHARMM primarily targets biological systems including peptides, proteins, prosthetic
groups, small molecule ligands, nucleic acids, lipids, and carbohydrates, as they occur in
solution, crystals, and membrane environments. CHARMM also finds broad applications
for inorganic materials with applications in materials design.
 CHARMM contains a comprehensive set of analysis and model building tools
 CHARMM achieves high performance on a variety of platforms including parallel
clusters and GPUs.
 CHARMM is actively maintained by a large group of developers led by Martin Karplus.
CFF: (Consistent force field) :

• Analytical derivatives of the various calculated quantities

with respect to the energy parameters help to facilitate the
computational procedures. The resulting agreement with
experiment is used as a measure of success of the energy
functions with optimized parameters, referred to as
“consistent force field” (CFF)
Aims of Theory:

The aim of the CFF development is a force field that is:

 broad, covering a relatively large number of differing functional
groups,
 accurate, achieved via accurate reproduction of the quantum
mechanical energy surfaces,
 consistent between differing phases and molecular environments,
 applicable to a wide range of molecular properties
Compass: (Condensed-phase optimized molecular
potentials for atomistic simulation studies) :
COMPASS) is a member of the consistent family of force fields
(CFF91, PCFF, CFF and COMPASS), which are closely related
second-generation force fields. COMPASS is a powerful force field
that supports atomistic simulations of condensed phase materials
It is the first Ab initio force field that has been parameterized and
validated using condensed-phase properties.
The latest enhancements to the COMPASS force field have
concentrated on parameterization of more than 45 inorganic oxide
materials and mixed systems.
COMPASS: Leading-Edge Science:
COMPASS development aims to achieve high accuracy in
prediction. The goal is to be able to predict properties of molecules,
both in isolation and in the condensed phase, with an accuracy
comparable with experiment
All of the parameters in COMPASS are derived in a consistent
manner so that, in principle, one can study very different systems
including interfaces and mixtures
Gromos: (Groningen Molecular simulation
package) :
The GROMOS961 package has been developed to facilitate research
efforts in the field of biomolecular simulation in a university environment.
The package acts as a test bed for developing new simulation methods, as
well as providing the tools required for routine modeling applications.
The GROMOS package has been developed by W. F. van Gunsteren and
co-workers since 1978 (at Harvard University (USA), University of
Groningen (The Netherlands), and ETH Zu¨rich (Switzerland)).
Because it has been designed for ease of extendability and the complete
source code is made available to research establishments for a nominal fee,
it has found widespread use (hundreds of licences in over 40 countries on
all continents).
• We present the newest version of the Groningen Molecular Simulation
program package, GROMOS96.
• GROMOS96 has been developed for the dynamic modeling of
(bio)molecules using the methods of molecular dynamics, stochastic
dynamics, and energy minimization as well as the path-integral formalism.
An overview of its functionality is given, highlighting methodology not
present in the last major release, GROMOS87
The Software :
 The software suite GROMACS (Groningen Machine for Chemical Simulation)
that was developed at the University of Groningen, The Netherlands, in the early
1990s. The software, written in ANSI C, originates from a parallel hardware
project, and is well suited for parallelization on processor clusters. By careful
optimization of neighbor searching and of inner loop performance, GROMACS
is a very fast program for molecular dynamics simulation. It does not have a
force field of its own, but is compatible with GROMOS, OPLS, AMBER, and
ENCAD force fields.
Reliability and Efficiency:

New members of the development team were provided with a means to assess
the status of the project.
It gave a concise overview of the project and a better understanding how parts
of the code should interact
It provided a framework for the logical development of the project. By
maintaining record of past decisions wasteful backtracking and revision could
be minimized.
Independent code reading
Independent code testing
Portability checking
Consistency checking
.

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