Course: CML801

(Molecular Modelling and Simulations: Concepts and Techniques)

 Why Molecular Modelling and Simulations?
• Understanding natural phenomena from science or optimizing
processes from engineering requires synchronized contributions
from theory, experiment and computation.

• In many cases, computer simulations based on fundamental theory

supplement experiment.

• But in many others cases, computer simulations are the enabling

tool to study and comprehension of complex systems and
phenomena that would otherwise be too expensive or dangerous,
or even impossible, to study by direct experimentation.
 Why Simulations?

Model
System

Theory
Real Perform Experiments

Test
Experimental
System Results

Theoretical
Prediction
 Length and Time Scales

Heavy Coarse
graining

F=ma

• Parameters obtained from smaller scale simulations can be fed into

larger scale simulations
 • The aim is to reproduce the phase-space trajectory of the
system as accurately as possible
• Sources of errors: Poor choice of the force-field, large dt,
inadequate integration algorithm

Phase-space Trajectory

Energy
p

r Simulation Time

7
 Atomistic MD (Classical)
• Uses Born-Oppenheimer Approximation
• Atoms are assumed in their ground electronic states

Born-Oppenheimer Approximation
𝑚𝑒
Total wavefunction, Ψ(𝐑 𝑖 , 𝐫𝛼 ) = Φ(R i )𝜙(𝐫𝛼 , 𝐑 𝑖 ) as 𝑀
→0

Φ(𝐑 𝑖 ) : Nuclei wavefunction

𝜙(𝐫𝛼 , 𝐑 𝑖 ) : Electron wavefunction parametrically depending on 𝐑𝑖

𝐻𝑇𝑜𝑡𝑎𝑙 = 𝐻𝑒𝑙𝑒𝑐𝑡𝑟𝑜𝑛𝑖𝑐 + 𝐻𝑁𝑢𝑐𝑙𝑒𝑎𝑟

𝐻𝑒 : Governs electronic motion (HF, DFT etc.)

𝑃𝐼2
𝐻𝑁 = σ𝐼 + U(RI): Governs nuclear motion or overall motion of the
2𝑀𝐼
atom (Newton's Law or Hamilton’s equations of motion; Molecular
Dynamics(MD)
Thermodynamics:
• Laws of thermodynamics
• Macroscopic properties, Thermodynamics Variables: ρ, P, T, V, M, E, S,…
Avogadro number of particles, NA=6.023 ⅹ 1023
• Thermodynamic Limit: N → ∞, V→∞
• Ignore molecular details

• Statistical Thermodynamics: We do care about the molecular

details, establish connection between molecular details (microscopic states) and
macroscopic properties. Microscopic state is defined as {r1(t), r2(t)…ri(t)…rN(t);
v1(t), v2(t)…vi(t)…vN(t)}

• Quantum Mechanics: System microscopic or macrostat state is defined by

ᴪ(r,t)
 Thermodynamics:

• Macrostate
(NVT), (NPT), (NVE), (µVT)
• Equation of state

Statistical Thermodynamics
• Microstate
{r1(t), r2(t)…ri(t)…rN(t);
v1(t), v2(t)…vi(t)…vN(t)}

• One macrostate can have

many-many microstates

Quantum Mechanics
Ψ(𝐑 𝑖 , 𝐫𝛼 ) = Φ(𝐑 𝑖 )𝜙(𝐫𝛼 , 𝐑 𝑖 )
 MOLECULAR DYNAMICS (MD) SIMULATIONS
• Ab-initio (AI) Molecular Dynamics: N~500, t~100ps
Both electronic as well as nuclear degrees of freedom
are considered, also involves QM theory
• All-Atom (AA) Molecular Dynamics : N~106, t~1µs
Only nuclear motion is considered, electrons are assumed to be in ground
electronic/vibrational states, only classical/statistical mechanics theories
are applicable
• Coarse-Grained (CG) Molecular Dynamics: N~109, t~1ms
Motion of coarsed-grained beads is considered,
only classical/statistical mechanics theories are
applicable

Depending upon the time- and length-scales and the details

of the system, the choice is yours! 13
1900: Inception of Quantum Mechanics ( By Planck)
1925: Birth of Quantum Mechanics (Schrodinger Equation, de Broglie
wave particle duality)

Pre-Quantum Mechanics:
(i) Newton (1642-1727) introduced law of motion

Second law:-
𝑑𝑝Ԧ 𝑑𝑣Ԧ 𝑑 2 𝑟Ԧ
𝐹Ԧ = =𝑚 = 𝑚 2 = 𝑚𝑎Ԧ
𝑑𝑡 𝑑𝑡 𝑑𝑡

(ii) Lagrange (1736-1813): Started with energy

𝑚 2
𝐾= 𝑥ሶ + 𝑦ሶ 2 + 𝑧ሶ 2 ; 𝑉 = 𝑉(𝑥, 𝑦, 𝑧)
2
𝑳𝒂𝒈𝒓𝒂𝒏𝒈𝒊𝒂𝒏: 𝐿(𝑥,ሶ 𝑦,ሶ 𝑧,ሶ 𝑥, 𝑦, 𝑧) = 𝐾(𝑥,ሶ 𝑦,ሶ 𝑧)ሶ − 𝑉(𝑥, 𝑦, 𝑧)
𝑳𝒂𝒈𝒓𝒂𝒏𝒈𝒆 𝑬𝒒𝒖𝒂𝒕𝒊𝒐𝒏 𝒐𝒇 𝒎𝒐𝒕𝒊𝒐𝒏
𝑑 𝜕𝐿 𝜕𝐿
= 𝑎𝑛𝑑 𝑠𝑖𝑚𝑖𝑙𝑎𝑟𝑙𝑦 𝑓𝑜𝑟 𝑦 𝑎𝑛𝑑 𝑧
𝑑𝑡 𝜕𝑥ሶ 𝜕𝑥
(iii) Hamilton (1805-1865):

Introduced 3 time−dependent coordinates, 𝑞j ; j = 1,2,3

𝜕𝐿
3 conjugate momenta, 𝑝j = ; j = 1,2,3
𝜕𝑞ሶ 𝑗
3

Hamilton′s function: 𝐻(𝑝1 , 𝑝2 , 𝑝3 , 𝑞ሶ 1 , 𝑞ሶ 2 , 𝑞ሶ 3 ) = ෍ 𝑝𝑗 𝑞ሶ 𝑗 − 𝐿

𝑗=1
𝑻𝒘𝒐 𝒆𝒒𝒂𝒖𝒕𝒊𝒐𝒏𝒔 𝒐𝒇 𝒎𝒐𝒕𝒊𝒐𝒏

𝜕𝐻 𝜕𝐻
= 𝑞ሶ 𝑗 𝑎𝑛𝑑 = −𝑝ሶ𝑗
𝜕𝑝𝑗 𝜕𝑞𝑗

(iv) Quantum Mechanics: H=K+V

෡ 𝛙 = 𝐄𝛙
𝐇 Schrodinger Equation (Time independent)
 First Law of Thermodynamics
The internal energy (U) of an isolated system is
constant (or conserved).

U=Constant for Isolated system

ADIABATIC/INSULATING WALL

SYSTEM
S
U=Const.
SURROUNDINGS
• The internal energy (U) of a system can be changed either
by doing work on the system or by heating the system

• The internal energy (U) of a system can also change if the

system is doing work or releasing heat into the
surroundings.

• Heat and work are equivalent ways of changing a system’s

internal energy.
To change the energy of the system by amount dU:

Ӎ + d𝑤
d𝑈𝑆𝑦𝑠 = d𝑞 Ӎ

Supply Do some
Heat Work
 Ӎ + d𝑤
d𝑈𝑆𝑦𝑠 = d𝑞 Ӎ

Supply Do some
Heat

SURROUNDINGS
Work
SYSTEM
Ӎ
U+dU
S
d𝑤
dU >0
ADIABATIC WALL
SURROUNDINGS

SYSTEM
S
U

SURROUNDINGS
Ӎ
d𝑞

Diathermal Wall
ADIABATIC WALL SYSTEM
U+dU
S

dU >0
ADIABATIC WALL
When energy is transferred to the When a system does work,
surroundings as heat, the transfer it stimulates orderly motion
stimulates random motion of the
in the surroundings.
atoms in the surroundings.
Transfer of energy from the
surroundings to the system makes
use of random motion (thermal
motion) in the surroundings.
 Entropy and Second Law of Thermodynamics

S
Equilibrium (Reversible)

Smax
dS=0

dS>0

time
Spontaneous
(Irreversible)

𝑑𝑆 > 0 (Spontaneous process(irreversible) in isolated system)

𝑑𝑆 = 0 (Reversible process in an isolated system)
 Thermodynamic Potentials

Four quantities called "thermodynamic potentials" are useful in the

chemical thermodynamics of reactions and non-cyclic processes.
They are internal energy, the enthalpy, the Helmholtz free energy
and the Gibbs free energy.

Δ𝑈 = 𝑞𝑉 Δ𝑈 = 𝑞𝑉

Δ𝐻 = 𝑞𝑃 Δ𝐻 = 𝑞𝑃

Δ𝐹 =? Δ𝐹 = 𝑤max

Δ𝐺 =? Δ𝐺 = 𝑤𝑎𝑑𝑑,max
 The Helmholtz and Gibbs energies
Consider a system in thermal equilibrium with its surroundings at a temperature T. When a
change in the system occurs and there is a transfer of energy as heat between the system and
the surroundings, the Clausius inequality
Criteria for spontaneity 𝑑𝑞Ӎ
𝑑𝑆 ≥ 𝑑𝑆 ≥ 0 for an isolated system
(Clausius inequality) 𝑇

Constant Volume Condition Constant Pressure Condition

𝑑𝑞Ӎ 𝑉 𝑑𝑞Ӎ 𝑃
𝑑𝑆 − ≥0 𝑑𝑞Ӎ 𝑉 = 𝑑𝑈 𝑑𝑆 −
𝑇
≥0 𝑑𝑞Ӎ 𝑃 = 𝑑𝐻
𝑇

𝑑𝑈 𝑑𝐻
𝑑𝑆 − ≥0 𝑑𝑆 − ≥0
𝑇 𝑇
𝑇𝑑𝑆 − 𝑑𝑈 ≥ 0 𝑇𝑑𝑆 − 𝑑𝐻 ≥ 0

𝑇𝑑𝑆 ≥ 𝑑𝑈 𝑇𝑑𝑆 ≥ 𝑑𝐻

Constant internal energy (dU=0) or constant At either constant enthalpy or constant entropy
entropy (dS=0) this inequality becomes

𝑑𝑆𝑈,𝑉 ≥ 0 𝑑𝑈𝑆,𝑉 ≤ 0 𝑑𝑆𝐻,𝑃 ≥ 0 𝑑𝐻𝑆,𝑃 ≤ 0

 CRITERIA FOR SPONTANEITY
Constant Volume Condition Constant Pressure Condition

Constant internal energy (dU=0) or constant At either constant enthalpy or constant entropy
entropy (dS=0) this inequality becomes

𝑑𝑆𝑈,𝑉 ≥ 0 𝑑𝑆𝐻,𝑃 ≥ 0

In a system at constant volume and constant The entropy of the system at constant pressure
internal energy (such as an isolated system), must increase if its enthalpy remains constant
the entropy increases in a spontaneous (for there can then be no change in entropy of
change. the surroundings).

𝑑𝑈𝑆,𝑉 ≤ 0 𝑑𝐻𝑆,𝑃 ≤ 0

If the entropy and volume of the system are The enthalpy must decrease if the entropy of
constant, then the internal energy must the system is constant, for then it is essential to
decrease in a spontaneous change. have an increase in entropy of the
i.e. if the entropy of the system is surroundings.
unchanged, then there must be an increase in
entropy of the surroundings, which can be
achieved only if the energy of the system
decreases as energy flows out as heat.
 CRITERIA FOR SPONTANEITY
Constant Volume Condition Constant Pressure Condition
𝑑𝑈 − 𝑇𝑑𝑆 ≤ 0 𝑑𝐻 − 𝑇𝑑𝑆 ≤ 0

These can be expressed more simply by introducing two more thermodynamic

quantities
Helmholtz Gibbs
Energy 𝐹 = 𝑈 − 𝑇𝑆 𝐺 = 𝐻 − 𝑇𝑆
Energy

When the state of the system changes at constant temperature, the two
properties change as follows:

𝑑𝐹 = 𝑑𝑈 − 𝑇𝑑𝑆 𝑑𝐺 = 𝑑𝐻 − 𝑇𝑑𝑆

Therefore the criteria of spontaneous change becomes as

𝑑𝐹𝑇,𝑉 ≤ 0 𝑑𝐺𝑇,𝑃 ≤ 0
Some remarks on the Helmholtz energy Some remarks on the Gibbs energy

1. The criterion of equilibrium, when neither 1. The criterion of equilibrium, when

the forward nor reverse process has a neither the forward nor reverse process
tendency to occur, is has a tendency to occur, is

𝑑𝐹𝑇,𝑉 = 0 𝑑𝐺𝑇,𝑃 = 0

2. Maximum work: It turns out that F carries

a greater significance than being simply a 2. Maximum Non-expansion work:
signpost of spontaneous change: the
change in the Helmholtz function is equal
to the maximum work accompanying a 𝑑𝐺 = 𝑑𝑤𝑎𝑑𝑑,max
process:

𝑑𝐹 = 𝑑𝑤max