Molecular Simulation

Molecular Simluation• Introduction:• Prerequisition: • A powerful computer, fast graphics

card,• An efficient way to solve

Schroedingers wave equation for many atoms,

• A reliable structure or structural model

Molecular Simluation• Structures or reliable model

structures:• X-ray crystallography• NMR spectroscopy• Homology modelling

Molecular Simulation• Where do we get the structures

from?• Databases• Brookhaven protein data base• Or homology models

Molecular Simulation• Homology modelling:

Molecular Simulation• Molecular Mechanics:• The Potential energy surface (PES):• Born-Oppenheimer approx. allows us to

separate electronic and nuclear motion • when nuclei move, the electrons re-adjust

quickly • energy of molecule is a function of the

positions of the nuclei • potential energy surface describes energy

of a molecule in terms of its structure

Molecular Simulation

Molecular Simulation• Structure • determined from the potential energy surface • minimum corresponds to an equilibrium structure • first order saddle point corresponds to a transition state for a

reaction • a reaction path is the steepest descent path connecting a

transition state to minima

• Dynamics • molecules move on the potential energy surface • dynamics can be treated classically or quantum mechanically • small amplitude motions - normal modes of vibration • large amplitude motions - trajectories, wave packets, reactions • statistical mechanics to connect microscopic to macroscopic

Molecular Simulation• Bond stretching• Valence angle bending• Torsions• Van der Waals Interactions• Electrostatic Interactions• Cross terms

Molecular Simulation• Bond Stretching and valence angle

bending

Molecular Simulations• Torsions

Molecular Simulation• Interaction of 2 point charges

Molecular Simulation• Van der Waals Interactions

Molecular Simulation• Force Field Energies• Geometry Optimisation• Thermodynamics

Molecular Simulation• Modern Force Fields

• CHARMM Biomolecules• CHARMm Bio and org. molecules• CFF/CVFF org. and bio molecules• GROMOS Biomolecules• MM2 organics• MM3 org. and bio molecules• OPLS all-atom and united atom version• SYBYL/TRIPOS org. and bio molecules