COMPUTATIONAL CHEMISTRY

Introduction
The term theoretical chemistry may be defined as the
mathematical description of chemistry.
Currently, there are two ways to approach theoretical
chemistry problems: computational theoretical chemistry and non-
computational theoretical chemistry.
Computational theoretical chemistry is primarily concerned
with the numerical computation of molecular electronic structures and
molecular interactions.
Non-computational quantum chemistry deals with the
formulation of analytical expressions for the properties of molecules
and their reactions.
 COMPUTATIONAL CHEMISTRY
The term computational chemistry is usually used when a
mathematical method is sufficiently well developed that it can be
automated for implementation on a computer.
Computational chemistry is the application of chemical,
mathematical and computing skills to the solution of interesting
chemical problems.
It uses computers to generate information such as properties of
molecules or simulated experimental results.
Very few aspects of chemistry can be computed exactly, but almost
every aspect of chemistry has been described in a qualitative or
approximate quantitative computational scheme.
 COMPUTATIONAL CHEMISTRY

The biggest mistake that computational chemists can make is to

assume that any computed number is exact.

However, just as not all spectra are perfectly resolved, often a

qualitative or approximate computation can give useful insight into
chemistry if you understand what it tells you and what it doesn't.
Computational chemistry has become a useful way to
investigate materials that are too difficult to find or too expensive to
purchase.
It also helps chemists make predictions before running the
actual experiments so that they can be better prepared for making
observations.
 COMPUTATIONAL CHEMISTRY
The quantum and classical mechanics as well as statistical
physics and thermodynamics are the foundation for most of the
computational chemistry theory and computer programs.

This is because they model the atoms and molecules with

mathematics.

Using computational chemistry software one can perform

following calculations:
Electronic structure determinations

Geometry Optimizations

Frequency calculations
 COMPUTATIONAL CHEMISTRY
 Defining transition structures and reaction paths

 Protein calculations (Eg. Docking, Folding, Conformation)

 Electron and charge distributions calculations

 Calculations of potential energy surfaces (PES)

 Calculations of rate constants for chemical reactions (Kinetics)

 Thermodynamic calculations- heat of reactions

energy of activation
 Calculation of many other molecular and balk physical

and chemical properties.

 COMPUTATIONAL CHEMISTRY
The most important numerical techniques are, molecular mechanics, semi-
empirical and ab-initio methods.
Definitions of these terms are helpful in understanding the use of
computational techniques in chemistry:
Molecular mechanics uses classical physics and empirical or semi-empirical
(pre­determined) force fields to explain and interpret the behavior of atoms
and molecules.
Semi-empirical techniques use approximations from empirical
(experimental) data to provide the input into the mathematical models.
ab-initio, (Latin for "from the beginning") a group of methods in which
molecular structures can be calculated using nothing but the Schrodinger
equation, the values of the fundamental constants and the atomic numbers of
the atoms present.
 A BRIEF HISTORY ON COMPUTATIONAL CHEMISTRY
1925 – Warner Heisenberg, Max Born, and Pascal Jordan develop matrix
mechanics
– Erwin Schrö dinger invents wave mechanics and non-relativistic
Schrö dinger equation
– Walter Heitler and Fritz London publish first calculations on
chemical bonding
1927 – Douglas Hartree publishes self–consistent field method
1930 – Vladimir Fock formulates Hartree–Fock theory
1947 – ENIAC is the first general–purpose computer to be built
1950 – Clemens Roothaan publishes LCAO theory
1951 – UNIVAC is the first commercial general–purpose computer
1955 – First ab initio calculation on 'large' molecule, N2
– Transistors replace vacuum tubes in computers
1964 – Pierre Hohenberg and Walter Kohn introduce density–functional
theory
1970 – John Pople introduces Gaussian (software)
1971 – First commercially available microprocessor (Intel 4004)
A BRIEF HISTORY ON COMPUTATIONAL CHEMISTRY
NOBEL PRIZES IN
COMPUTATIONAL CHEMISTRY

-Walter Kohn (1998)

"FOR HIS DEVELOPMENT OF

DENSITY-FUNCTIONAL THEORY"

-John Pople (1998)

"FOR HIS DEVELOPMENT OF

COMPUTATIONAL METHODS IN
QUANTUM CHEMISTRY"

-Martin Karplus, Michael Levitt,

and Arieh Warshel (2013)

"FOR THE DEVELOPMENT OF

MULTISCALE MODELS
FOR COMPLEX CHEMICAL SYSTEMS"
 TOOLS AND PACKAGES (HARDWARE /SOFTWARE)

Many self-sufficient computational chemistry software packages exist.

Some include many methods covering a wide range, while others concentrate
on a very specific range or even on one method.

DL_POLY

DL_POLY is a general purpose classical molecular dynamics (MD)

simulation software developed at Daresbury Laboratory by I.T. Todorov and
W. Smith

ADF

Modeling suite: ReaxFF, UFF, QM-MM with Amber and Tripos force fields,
DFT and semi-empirical methods, conformational analysis with RDKit, partly
GPU-accelerated
 TOOLS AND PACKAGES (HARDWARE /SOFTWARE)
AMBER (Assisted Model Building with Energy Refinement)
For molecular mechanics and molecular dynamics
CHARMM
For molecular mechanics and molecular dynamics
COSMOS
Hybrid QM-MM COSMOS-NMR force field with fast semi-empirical
calculation of electrostatic and/or NMR properties
Discovery Studio
Comprehensive life science modeling and simulation suite of applications
focused on optimizing drug discovery process: small molecule simulations,
QM-MM, pharmacophore modeling, QSAR, protein-ligand docking, protein
homology modeling, sequence analysis, protein-protein docking, antibody
modeling, etc.
 TOOLS AND PACKAGES (HARDWARE /SOFTWARE)
CHEMKIN
Chemical reaction kinetics.
GROMOS
Intended for biomolecules
Materials Studio
Environment that brings materials simulation technology to desktop
computing, solving key problems in R&D processes
MOE
Molecular Operating Environment (MOE) Intended for biomolecules
ORCA
Molecular dynamics simulation program to explore free energy surfaces
in biomolecular systems at the atomic level
 TOOLS AND PACKAGES (HARDWARE /SOFTWARE)
Spartan
Small molecule (< 2,000 a.m.u.) MM and QM tools to determine
conformation, structure, property, spectra, reactivity, and selectivity.
TeraChem
High performance GPU-accelerated ab initio molecular dynamics
and TD/DFT software package for very large molecular or even
nanoscale systems. Runs on NVIDIA GPUs and 64-bit Linux, has heavily
optimized code.
Gaussian16 and GaussView
Extremely powerful general and advanced quantum chemistry
package.
TOOLS AND PACKAGES (HARDWARE /SOFTWARE)
Workstation
TOOLS AND PACKAGES (HARDWARE /SOFTWARE)
Configuration
COMPUTATIONAL CHEMISTRY
Cluster Computers
 MODELS, APPROXIMATIONS AND REALITY
 One of the most commonly used construct is a Model.
 A model is a simple way of describing and predicting scientific
results, which is known to be an incorrect or incomplete
description.
 Models might be simple mathematical descriptions or completely
non mathematical.
 Models are very useful because they allow us to predict and
understand phenomena without the work of performing the
complex mathematical manipulations dictated by a rigorous
theory.
 A very useful model is the Lewis dot structure description of
chemical bonding. It has its own advantage and disadvantages.
 It is not a complete description of the molecules involved since it
does not contain the kinetic energies of the particles or Columbic
interactions between the electrons and nuclei.
 MODELS, APPROXIMATIONS AND REALITY
 The theory of quantum mechanics, which accounts correctly
for these factors, does predict that only two electrons can have
the same spatial distribution (one of α-spin and one of β-spin).
 This results in the Lewis model being able to predict chemical
bonding patterns and give an indication of the strength of the
bonds (single bonds, double bonds, etc.). However, none of the
quantum mechanics equations are used in applying this
technique.
 Approximations are another construct that is often
encountered in chemistry. Even though a theory may give a
rigorous mathematical description of chemical phenomena,
the mathematical difficulties might be so great that it is just
not feasible to solve a problem exactly.
 MODELS, APPROXIMATIONS AND REALITY
 If a quantitative result is desired, the best technique is often to
do only part of the work .
 One approximation is to completely leave out part of the
calculation. Another approximation is to use an average rather
than an exact mathematical description.
 Some other common approximation methods are variations,
perturbations, simplified functions, and setting parameters to
reproduce experimental results.
 Quantum mechanics gives a mathematical description of the
behavior of electrons that has never been found to be wrong.
However, the quantum mechanical equations have never been
solved exactly for any chemical system other than the
hydrogen atom.
 MODELS, APPROXIMATIONS AND REALITY
 Thus, the entire field of computational chemistry is built around
approximate solutions.
 Some of these solutions are very crude and others are expected
to be more accurate than any experiment that has yet been
conducted. There are several implications of this situation.
 First, computational chemists require a knowledge of each
approximation being used and how accurate the results are
expected to be.
 Second, obtaining very accurate results requires extremely
powerful computers.
 Third, if the equations can be solved analytically, much of the
work now done on PC.
 MODELS, APPROXIMATIONS AND REALITY
 This discussion may well leave one wondering what role reality
plays in computation chemistry. Only some things are known
exactly.
 For example, the quantum mechanical description of the hydro
gen atom matches the observed spectrum as accurately as any
experiment ever done.
 If an approximation is used, one must ask how accurate an
answer should be. Computations of the energetics of molecules
and reactions often attempt to attain what is called chemical
accuracy, meaning an error of less than about 1 kcal/mol.
 This is sufficient to describe van der Waals interactions, the
weakest interaction considered to accurate most chemistry. Most
chemists have no use for answers more accurate than this.
 MODELS, APPROXIMATIONS AND REALITY
 A chemist must realize that theories, models, and approximations
are powerful tools for understanding and achieving research
goals.
 Chemists are advised to develop an understanding of the nature
of computational chemistry approximations and what results can
be trusted with any given degree of accuracy.
 Applications of Computational Chemistry. (Assignment)
- Materials Design
- Drug Design
- Molecular Quantum Mechanics
 FUNDAMENTAL PRINCIPLES
Energy
Energy is one of the most useful concepts in science .
If we know the energetics of a system, then we can easily predict the
total nature of state of the system and its process.
The molecular stability is closely related to energy.
Stability = 1 / Energy
The total energy of the system can be spited into two parts namely
Kinetic Energy (KE) and Potential Energy (PE).
Again KE can be further separated into Vibrational, Translational,
Rotational energies.
The PE is expressed purely by Coulombs law of interaction.
In formulating a mathematical representation of molecules, it is
necessary to define a reference system which has zero of energy.
 FUNDAMENTAL PRINCIPLES
Usually, the total energy of a system is subdivided into kinetic
energies of all particles and potential energies of the interactions
between them.
 2 electrons
2 nuclei
1 2 e2 electrons nuclei
ZA e2 electrons electrons 1 e2 nuclei nuclei
Z AZB
H 
2me
 i
 
2
i
2
 A MA
A 
4 0
 
i A

riA 4 0 i
  j r  4  
A

B RAB
ij 0

where
ZA-Nuclear charge, MA-Mass of nucleus A, me-Mass of electron,
RAB-Distance b/w nuclei A and B.
rij-Distance between electrons i and j,
riA-Distance between electron i and nucleus A,
ε0-Permitity of free space,
ђ-Planck constant.
 FUNDAMENTAL PRINCIPLES
 The zero of energy corresponds to the case when all the terms are
zero.
 Kinetic energy is zero when velocity is zero, while the Coulomb
interaction energy is zero when particles are infinitely separated
from each other.
 Thus, the zero of energy corresponds to the case when all the
particles are infinitely far away from each other and not moving.
 In accordance with that choice of the zero of energy, the energy of
any stable molecular system in the modeled.
 A few molecular mechanics methods use chemical standard states as
zero energy, but most use a stainless molecule as zero energy.
 FUNDAMENTAL PRINCIPLES
Electrostatics
Electrostatics is the study of interactions between charged
objects.
It is very important to the understanding of interactions of
electrons, which is described by a wavefunction or electron density.
The central pillar of electrostatics is Coulombs law, which is the
mathematical description of how like charges repel and unlike
charges attract.
The most simplified Coulombs law for energy and force can be
given by,
E = q1q2/r12
F = q1q2/r212
q1q2 are point charges and r12 distance between two charges.
 FUNDAMENTAL PRINCIPLES
 Another very useful function from electrostatics is the
electrostatic potential φ.
 The electrostatic potential is a function that is denoted at
every point in three dimensional real space.
Atomic Units
Basic units are converted into simple atomic units.
Atomic units are simplified by fixing many basic units equal to ‘1’
It helps to minimize the mathematical complication and error.
This simplification does not affect the theoretical results.
 FUNDAMENTAL PRINCIPLES
Thermodynamics
Thermodynamics is one of the most well-developed
mathematical descriptions of chemistry.
It is the field of thermodynamics that defines many of the
concepts of energy, free energy and entropy.
Various Thermodynamic properties can be computed.
The result of computations might be internal energies, free-
energies, and so on, depending on the computation done.
The computational software does not always make it obvious
on which energy is being computed, either thermodynamic or
theoretical energy.
 BASIC OF QUANTUM CHEMISTRY
 QM gives a correct mathematical description for electrons.
 QM can predict any property of an individual atom or
molecule exactly or approximately.
 Exact solutions can be derived to one electron system.
 Approximate solution can be given to many electron system.
 There are many approximations are there in application. The
choice of approximation is depends upon problem that we
need to solve, level of accuracy and computational facility.
 Schrodinger equation is the central part in QM and in
computational chemistry.
Ĥ ψ=Eψ
E-Total energy of the system, ψ=n-electron wave function.
Ĥ -Hamiltonian (Kinetic and Potential energies of electron and nucleus)
 BASIC OF QUANTUM CHEMISTRY
 This is a probabilistic description of electron behavior. It can
describe the probability of electrons being in certain locations,
but it cannot predict exactly where electrons are located.
 The wave function is also called a probability amplitude because
it is the square of the wave function that yields probabilities.
 The quality of the wave function as follows such as,
 it must be continuous,
 single-valued,
 normalizable,
 antisymmetric with respect to the interchange of electrons.
 The mathematical foundation of Ĥ -Hamiltonian as follows,
 2 electrons
2 nuclei
1 2
H 
2me
 i
 
2
i
2

A MA
A 

e2 electrons nuclei
ZA e2 electrons electrons
1 e2 nuclei nuclei
Z AZB
4 0
 
i A

riA 4 0
 i
  j

rij 4 0
 
A

B RAB
 BASIC OF QUANTUM CHEMISTRY
 Once the wave function has been determined, then any property
of the individual molecule can be determined.
 Exact wave functions give exact results. Approximate wave
functions give approximate results.
 Prediction of exact wave function is based on variation principle.
Using those wave functions one can able to calculate the
properties.
 Every operator is associated with a property, and if it is allowed
to operate upon the wavefunction leads to give the respective
property.
 Different operators gives different properties like dipole
moment, electron density.
Example:  
 
Energy Operator E  i Momentum Operator p  i 
t x
 BASIC OF STATISTICAL MECHANICS
 Statistical mechanics is a branch of theoretical chemistry.
 By using probability theory to study the average behaviour of a
mechanical system, where the state of the system is uncertain.
 Statistical mechanics is the mathematical means to calculate the
thermodynamic properties of bulk materials from a molecular
description of the materials.
 A common use of statistical mechanics is in explaining the
thermodynamic behaviour of large systems. This branch of
statistical mechanics, which treats and extends classical
thermodynamics, is known as statistical thermodynamics or
equilibrium statistical mechanics.
 Statistical mechanics computations are often tacked onto the end of
ab initio vibrational frequency calculations for gas-phase properties
at low pressure.
 BASIC OF STATISTICAL MECHANICS
 Statistical mechanics can also be used beyond equilibrium.

 An important sub-branch known as non-equilibrium statistical

mechanics deals with the issue of microscopically modeling the
speed of irreversible processes that are driven by imbalances.
 Computations of statistical mechanics associated properties can be
simulated at the end of ab initio vibrational frequency calculations
for gas-phase properties at low pressure.
 For condensed-phase properties, often molecular dynamics or
Monte Carlo calculations are necessary in order to obtain statistical
data. The following are the principles that make this possible.
 BASIC OF STATISTICAL MECHANICS

 In quantum mechanics, the wave function contains all dynamic

information about a system, such as its energy, the electron density,
the dipole moment, and so on.
 Once we know the wavefunction of an atom or molecule, we can
extract from it all the dynamical information possible about the
system.
 Similarly, In statistical mechanics, another term is there called
Partition function. It contains all the thermodynamic information
about the system, such as its internal energy, entropy, heat capacity,
and so on. If we exact partition function of a system, then we can
calculate statistical thermodynamic properties.
 BASIC OF STATISTICAL MECHANICS
The Boltzmann distribution
The single most important result in the whole of statistical
thermodynamics is the Boltzmann distribution, the formula that tells
us how to calculate the numbers of molecules in each state of a system
at any temperature.

Here Ni is the number of molecules in a state with energy Ei,

 N is the total number of molecules, k is Boltzmann’s constant, a
fundamental constant with the value 1.381 × 10−23 J K−1,
 T is the absolute temperature.
 Boltzmann’s constant k.
 The gas constant R are related by R = Nk.
 The term in the denominator, q, is the partition function .
 BASIC OF STATISTICAL MECHANICS
Finally, we can represent as,

There are many statistical thermodynamic functions namely,

 Translational partition function,
 Rotational partition function
 Vibrational partition function
 Electronic partition function
All these can be computationally calculated from their respective
mathematical formulation.
COMPUTATIONAL CHEMISTRY