11 March 2023

Computational Chemistry I
Dr Krishna K. Govender
JOB 4205
[email protected]
Computational Chemistry
•Computational (chemistry education)
• Use computational tools to help increase student understanding of
material already covered in various courses

•(Computational Chemistry) education

• Teach students about computational chemistry (molecular modelling)
itself, in both courses and research projects

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Computational Chemistry
Why use molecular modelling?
1. Determine molecular geometries
By determining the 3-D geometry of a molecule, chemists gain knowledge
of the bond lengths, bond angles, dihedral angles and other geometrical
parameters characteristic to a given molecule.

2. Calculate reaction rates and equilibria

Determining a reaction rate constant of a chemical reaction allows chemists
to quantify the rate and direction of the reaction.

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Computational Chemistry
Why use molecular modelling?
3. Determine properties of molecules
Various algorithms and computer programs can be used to calculate the
chemical, physical and structural properties of different molecules, allowing
scientists to develop safe and effective chemical agents.
4. Assists with analysing and understanding experimental data
Some experiments can be so complicated that it’s almost impossible to
analyse the data without using some sort of algorithm. This is why chemists
use computational chemistry (molecular modelling) as an analytical tool to
analyse experimental data and understand results.
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Computational Chemistry
Why use molecular modelling?
5. Predict properties of unknown/hazardous molecules
While the presence of certain chemicals can be verified by chemical
reactions, some molecules cannot be identified this way.

6. Enable the synthesis of new compounds efficiently

Since computational chemistry (molecular modelling) can be used to
predict reaction mechanisms of new experiments and properties of
unknown molecules, it facilitates the efficient synthesis of new compounds.

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Computational Chemistry
Why use molecular modelling?
7. Widely used in pharmaceuticals
Chemistry plays a critical role in the pharmaceutical industry, from material
testing to quality control. Computational chemistry (molecular modelling)
plays an important role when it comes to designing safe and effective
drugs.

8. Developing advancing modern scientific approaches

The advances in technology has resulted in faster and more effective
computational methods allowing chemists to generate meaningful data in
shorter periods of time.
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Computational Chemistry
Why use molecular modelling?
9. Provides critical data without spending too much time or financial resources
Some chemical reactions require multiple steps and a variety of expensive
compounds. To avoid spending too much time or finances on conducting a
chemical experiment, scientists use computational chemistry to obtain the data
first before going to the lab.

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Methods
1. Molecular Mechanics

2. Hartree-Fock

3. Semi-empirical

4. Density Functional Theory

[1] Errol G. Lewars, Computational Chemistry: Introduction to the Theory and Applications of Molecular and Quantum Mechanics, 2nd edition 8
Molecular Mechanics
• Based on the model of a molecule as being a collection of balls (atoms)
held together by springs (bonds)

• It is known as a force field

• All bonds, angles and dihedral angles are parameterized against either
experimentally available data or from electronic structure calculations e.g.,
Merck Molecular Force Field [2] and Quantum Mechanical Force Field [3]
[2] T. A. Halgren J. Comput. Chem. 14, 490 (1996) 9
[3] C. S. Ewig, R. Berry, U. Dinur, J. R. Hill, M. G. Hwang, H. Li, C. Liang, J. Maple, Z. Peng, T. P. Stckfisch, T. S. Thacher, L. Yan, X. Ni, and A. T. Hagler J. Comput. Chem. 22, 1782 (2001)
Molecular Mechanics
• Assumes the total energy of a molecule arises from a few, specific
interactions within the molecule.
• These include:
• Stretching or compressing of bonds beyond their equilibrium bond lengths and
angles
• Torsional effects of twisting about single bonds
• Van der Waals attraction or repulsion of atoms that are close together
• Electrostatic interactions between partial charges in a molecule due to polar
bonds Bonded Non-bonded

Etotal = ∑Estr + ∑Ebend + ∑Estr-bend + ∑Eoop + ∑Etor + ∑Evdw + ∑Eelec

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Molecular Mechanics
• Estr represents the energy required to stretch or compress a bond between two
atoms

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Molecular Mechanics
• Ebend is the energy required to bend from its equilibrium angle θ0

• θijk is the instantaneous bond angle

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Molecular Mechanics
• Estr-bend is the energy that considers the observation that when a bond is bent,
the two associated bond lengths increase

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Molecular Mechanics
• Eoop is the energy required to deform a planar group of atoms from its
equilibrium angle, ω0, usually equal to zero

• The out of plane term is also called the improper torsion in some force fields

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Molecular Mechanics
• The out of plane term is called the
improper torsion, because like a
dihedral torsion the term depends on
four atoms, but the atoms are
numbered in a different order
• Force fields differ greatly in their use
of out of plane terms
• Most use out of plane terms for
carbonyl carbon and amide nitrogen
in peptide bonds

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Molecular Mechanics
• Etor is the energy of
torsion needed to
rotate about bonds

• These are usually

important for single
bonds because
double and triple
bonds are too rigid
to permit rotation

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Molecular Mechanics
• Torsion energies are rationalized by some as a repulsion between bonds of
groups attached to a central, rotating bond (i.e., C-C-C-C frameworks)

• Torsion terms were originally used as a fudge factor to correct for the other
energy terms when they did not accurately predict steric energies for bond
twisting

• For example, the interactions of methyl groups and hydrogens on the “front”
and “back” carbons of butane were thought to be Van der Waals in nature,
but that alone gave inaccurate values for the steric energy

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Molecular Mechanics
• Van der Waals interactions
liquefaction of non-polar gases
like O2 and N2, also govern the
energy of interaction of non-
bonded atoms within a molecule

• These interactions contribute to

the steric interactions in molecules
and are often the most important
factors in determining the overall This is also known as the Lennard Jones
molecular conformation (shape) potential
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Molecular Mechanics
• Electrostatic interactions take place when bonds in a molecule are polar
which results in partial electrostatic charges residing on the atoms.

• A molecule is polar when atoms do not share electrons equally

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Molecular Mechanics Force Fields
• AMBER
• GROMOS
• CHARMM
• MM2
• MM3
• UFF
• OPLS2005
• OPLS4
• CVFF
• ENZYMIX
• Others
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Quantum Mechanics
෡ = 𝐸Ψ
𝐻Ψ
Ĥ = Hamiltonian operator N.B. Can only be solved
𝛹 = Wavefunction exactly for a single electron
system (hydrogen atom)
E = Energy

ℏ2 𝑑 2 𝛹 𝑥
− 2
+ 𝑉 𝑥 𝛹(𝑥) = 𝐸𝛹(𝑥)
2𝑚 𝑑𝑥
ℎ 6.626*10-34 m2kg/s
ℏ=
2𝜋

𝐾𝐸 + 𝑃𝐸 = 𝐸
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Ab initio
• Ab initio is latin for “from first principles” or “from the beginning”

• It means that you compute the electronic state energies and other physical
properties, as a function of the nuclei, from first principles without the use or
knowledge of experimental input

• It solves the Schrödinger equation for a molecule and gives the energy and
wave function

• The computational complexity grows exponentially with the number of atoms

[1] Errol G. Lewars, Computational Chemistry: Introduction to the Theory and Applications of Molecular and Quantum Mechanics, 2nd edition 22
Hartree-Fock
• It is typically used to solve the time independent Schrödinger equation for a
multi-electron atom or molecule

• Since there are no known analytic solutions for many-electron systems the
problem is solved numerically

• It is easy to code and hence is the dominant approximate method

• Due to nonlinearities introduced by the approximation the equations are solved

using a nonlinear method such as iteration, which gives rise to what’s called
“self-consistent field method”
[1] Errol G. Lewars, Computational Chemistry: Introduction to the Theory and Applications of Molecular and Quantum Mechanics, 2nd edition 23
Hartree-Fock

HF/6-31G

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Hartree-Fock
• It breaks down a multi-electron wave function into a set of one-electron wave
functions, called molecular orbitals

• The prevalent concept of molecular orbitals, which is in the mind of every chemist,
originates from the Hartree-Fock theory

• The momentum operator is assumed to be completely non-relativistic

• It has insufficient accuracy because it does not account for electron correlation

• As a result, researchers rarely use it directly these days

[1] Errol G. Lewars, Computational Chemistry: Introduction to the Theory and Applications of Molecular and Quantum Mechanics, 2nd edition 25
Hartree-Fock
• It is the foundation theory behind most of the popular electronic structure methods

• Many of the popular electronic structure methods start with the Hartree-Fock
equation and then fix its electron correlation

• These are known as post-Hartree Fock methods:

• Configuration interaction
• Coupled cluster
• Multi-configuration time-dependent Hartree
• Møller-Plesset perturbation theory
• Quadratic configuration interaction
• Quantum chemistry composite methods
[1] Errol G. Lewars, Computational Chemistry: Introduction to the Theory and Applications of Molecular and Quantum Mechanics, 2nd edition 26
THE END

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