Molecular and Quantum Mechanics in drug design

1. Presented by:
Ajay Kumar (0181PCH004)
Under the guidance of
Dr. Salahuddin

2. • Molecular Mechanics in drug design
• Quantum Mechanics in drug design
• Discreteness between both QM & MM
• Applications
• Density Functional Theory (DFT)
• Semi-Empirical Method
• Reference

3. • Molecular Mechanics is a computational
method that computes the potential energy
surface for a particular arrangement of atoms
using potential functions that are derived using
classical physics.

5. • The basic functional form of an inter-atomic potential
encapsulates both bonded terms relating to atoms that
are linked by covalent bonds, and non-bonded. The
specific decomposition of the terms depends on the
force field, but a general form for the total energy in
an additive force field can be written as
• Etotal = Ebonded + Enonbonded
• Where the components of the covalent and non-
covalent contributions are given by the following
summations:
• Ebonded = Ebond + Eangle + Edihedral
• Enon-bonded = Eelectrostatic + Evander waals

6. • AMBER (Assisted Model Building and Energy
Refinement)
• CHARMM (Chemistry at Harvard Molecular
Mechanics)
• GROMOS (Gromningen Molecular Simulation
package)
• OPLS (Optimized Potential for Liquid Simulations)
• CFF (Consistent Force Field)
• COMPASS (Condensed-phase Optimized Molecular
Potentials for Atomistic Simulation Studies)
• MMFF (Merck Molecular Force Field) etc.

7. Parameters Quantum
Mechanics
Molecular
Mechanics
Molecular Size Small Large
Principle
Calculations
Electric Energy Nuclear Energy
Time Required Days Minutes/Hours
Accuracy High Low
Data Required Computational Computational
Cost Affairs High Low

8. • To Calculate The Geometries and Energies
• Computing Enthalpies of Bond Formation or
Breaking
• In Structure Based Drug Designing (Docking
Studies)
• To Monitor Reaction Path
• To Calculate Frequencies

9. • The word quantum comes from Latin
{“Quantus”= How much?}
• Quantum Mechanics defines the behaviour of
nuclei and electrons and it also explains the
molecular interactions in terms of distribution
and motion. It is necessary to describe the
quantized energy levels and to understand the
bonding electronic orbitals of atoms and
molecules.

10. • DFT is based not on the wave function, but
rather on electron probability density function
or electron density function, commonly called
simply the electron density or charge density.
• Density functional theory has its conceptional
roots in the Thomas-Fermi model.
• They used a statistical model to approximate
the distribution of electrons in an atom.

11. • Semi-empirical quantum chemistry method
make many approximations and obtain some
parameters from empirical (Experimental)
data.
• They are very important in computational
chemistry for treating large molecules.
• The use of empirical parameters appears to
allow some inclusion of electron correlation
effects into the methods.

12. Advantages of Semi-Empirical Method
• Semi-empirical calculations are very fast
• Medium-sized systems (hundreds of atoms)
Disadvantages
• Depend on experimental data
• Small systems
• Low accuracy

13. • Leach A. R.; 2001; Molecular Modeling principles and Applications;
Second edition; Pearson Hall; England; pp 1-127.
• Young D. D.; 2009; Computational Drug Design: A Guide for
Computational and Medicinal Chemists; John Wiley & Sons, Inc.; New
Jersey; pp 119-123, 187-194.
• Atkins P., Freidman R.; 2005; Molecular Quantum Mechanics; Fourth
edition; Oxford University Press Inc.; New York; pp 249, 250, 288-338.
• Raha K., Peter M., Ning Yu B., Wollcott A., Westerhoff L., Merz Jr K.;
2007; The Role Of Quantum Mechanics In Structure-based Drug Design;
Drug Discovery Today; Volume 12; no. 17/18; pp 725-731.
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