Computational Chemistry

Dr. Anjali Devi J S

Guest Faculty
School of Chemical Sciences
MG University

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Computational Chemistry
• Also known as Molecular modelling.

Computational Chemistry is a set of techniques for investigating

chemical problems on a computer.

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Questions Commonly Investigated Computationally
• Molecular geometry:
The shape of the molecules- bond lengths, angles, and dihedrals.

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Questions Commonly Investigated Computationally
• Energies of molecules and Transition states:
This tells us which isomer is favoured at equilibrium and how fast a
reaction should go.

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Questions Commonly Investigated Computationally
• Chemical reactivity

For example, Identifying electrophilic sites and nucleophilic sites and predict
where various kinds of reagents will attack a molecule.
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Questions Commonly Investigated Computationally
• IR, UV, and NMR spectra

These can be calculated, if

the molecule is unknown,
someone trying to make it
knows what to look for.

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Questions Commonly Investigated Computationally
• The interaction of substrate with enzyme

Seeing how molecules fit into active sites of a enzyme

(one approach to design better drugs.
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Questions Commonly Investigated Computationally
• The physical properties of substances
These depends on the properties of individual molecules and the molecule
interact in the bulk material.

Example: The strength and m.p of polymer depends on how well the
monomers fit together and how strong the force between them. 8
Tools of Computational Chemistry

Molecular Semiempirical
Ab initio calculations
Mechanics
calculations
(MM) (SE)

Density Molecular
functional dynamics
calculations calculations
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(1) Molecular Mechanics
• Based on the model of a molecule as collection of balls (atoms) held
together by springs (bonds)

Geometry optimisation: Identifying the geometry of molecule (having

lowest energy) by changing the geometry until the lowest energy is
calculated. 10
(1) Molecular Mechanics (Contd.)
• Molecular mechanics is fast:
A large molecule (eg: steroid like cholesterol C27H46O ) can be optimised
in seconds on a powerful desktop computer (a work station).

Cholesterol 11
 (2) Ab initio Calculations
• Ab initio is from the Latin: “from first principles”
• Based on Schrödinger equation.
The ab initio method solve Schrödinger equation for a
molecule and give energy and wavefunction.

Schrödinger
Energy and Electron
Equation of
wave function distribution
molecule

How Polar the molecule?

Where is Reaction centre of molecule?
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(2) Ab initio Calculations (Contd.)
• Ab initio Calculations are slow.
Geometry and spectra of simple molecule (propane ) can be calculated
in minutes on a premium type machine.

Propane
But steroids take weeks!! 13
(3) Semiempirical calculations
• Based on Schrödinger equation (like ab initio) but parametrized with
experimental values (empirical=experimental).
• Mixing of theory and experimental (It makes method is “semiempirical”)
• Parameterization: The plugging of experimental values into a
mathematical procedure to get the best calculated value.

Here, more approximations are made in solving Schrödinger equation, and

the very complicated integrals (that must be calculated in ab initio methods
are not actually evaluated in Semi empirical calculations.
Instead, the program daws a library of integrals that was compiled by finding
the best fit of some calculated entity (eg: energy) to experimental value 14
(3) Semiempirical calculations (Contd.)
• Semi empirical calculations are slower than molecular mechanics but
much faster than ab initio calculations.

Ab initio Semiempirical Molecular

Calculations calculations Mechanics

slow fast

A minute on In seconds on
Cholesterol- Several Weeks a desktop
premium type
Geometry On Pentium type machine computer
machine 15
optimisation
(4) Density functional Calculations
• often called density functional theory (DFT) calculations.
• Based on Schrödinger equation (like ab initio and semiempirical
methods).

DFT does not calculate wavefunction but rather

derives the electron distribution (electron density
function) directly.

A Functional is a mathematical entity related to a function.

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(4) Density functional Calculations (Contd.)
• DFT calculations are faster than ab initio but slower than
semiempirical calculations

Ab initio DFT Semiempirical Molecular

Calculations calculations calculations Mechanics

slow fast

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(4) Density functional Calculations (Contd.)
• DFT is relatively new: DFT computational chemistry goes back to
1980s. Computational chemistry with SE and ab initio were done in
1960s.
Ab initio
Calculations
DFT
Semiempirical calculations
calculations
1980s
1960s
Time (years)

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(5) Molecular Dynamics
• Apply the laws of motion to molecules.
• Thus, one can simulate the motion of an enzyme as it changes shape
on binding to a substrate, or the motion of a swarm of water
molecules around a molecule of solute.

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(5) Molecular Dynamics (Contd.)

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Uses of Computational chemistry
• Pharmaceutical industry –to explore drug-biomolecule interactions.
• Material science-properties of solids (material science).

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Advantages of Computational Chemistry
• Cheap
• Fast
• Environmentally safe

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Thank You

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