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