Molecular mechanics and quantum mechanics are the main computational methods for calculating molecular energies. Molecular mechanics uses empirical parameters derived from experimental data to model intermolecular interactions and calculate conformational energies quickly, though it cannot represent bond breaking and forming. Quantum mechanics uses first principles to model electronic structure and can reproduce experiments without parameters, but is more computationally expensive. Molecular mechanics force fields represent bond stretching, angle bending, torsions, and van der Waals interactions to model potential energy surfaces based on the Born-Oppenheimer approximation.

1. 1
Methods of Molecular Modelling
Molecular Mechanics
&
Quantum Mechanics
Abhijeet Kadam
TSEC
BioTechnology

2. 2
Energy Calculations
● Every molecule had some energy content and
energy level
● 3 major Theoretical computational methods of
calculating energies of molecules are :
– Imperical method – [ Molecular Mechanics ]
– Semi Imperical method – [ Quantum Mechanics ]
– Ab-Initio method – [ Quantum Mechanics ]
● 1 & 2 – rely on embedded emperical parameters
● 3 – capable of reproducing an Expt. Without
parameters

3. 3
Some types of molecular and
Intermolecular energies
● Electronic energy – UV – QM
● Protonation energy – QM
● Conformational energy – NMR – QM – MMech
● Solvation energy – QM – Mmech
● Sublimation energy – Mmech – QM
● Crystallization energy – Mmech
● Binding energy – Mmech – QM

4. 4
Molecular Mechanics
● Less complicated, fast, able to handle large
systems
● Can give extremely accurate energies if proper
parameters are available
● Major disadvantage – parameters are derived
from ground state only
– And cannot represent geometry in bond making and
bond breaking

5. 5
Principles
● Wokrs on principle of vibrational spectroscopy
– Bonds have natural length and natural angles
– Molecules will always adopt geometry that can best
reach the natural value
● When natural values cannot be acheived, there
is strain
– Hence van der waal potential function can mesure
this strain energy

6. 6
History
● Basic idea of Molecular mechanics – 1930
● Serious work started – 1946
● Calculations use the – Born-Oppenheimer
aproximation
– It describes energy of molecule in terms of nuclear
position
– Called as potential energy surface

7. 7
Progress
● Molecular mechanics calculations then employ
an empherically derived set of equations from
the Born-Oppenheimer surface
– Where mathematical form is derived from basic
mechanics
● This function of potential energy – called as
force feild
– Has adjustable parameters

8. 8
Formulae
● General Molecular Mechanics force feild is
based on Westheimer method
● Includes functions for
– Bond streaching
– Angle bending
– Torsion angle
– Vander waal interactions

9. 9
Formulae
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● Sum of all these gives Steric energy of moleculed

10. 10
● MM programs have some form of molecular
mechanics builtin
– Ex – Llingers MM2 and MM3 force feilds for Small
molecules
● Energy Minimization
– Inolves successive Iterations
– With full geometry
– All parameters defining geometry are modified in
small increments till it reaches Global Minima.