Molecular Simulation

Molecular Simluation Introduction: Introduction: Prerequisition: Prerequisition: A powerful computer, fast graphics card, A powerful computer, fast graphics card, An efficient way to solve Schroedingers wave equation for many atoms, An efficient way to solve Schroedingers wave equation for many atoms, A reliable structure or structural model A reliable structure or structural model

Molecular Simluation Structures or reliable model structures: Structures or reliable model structures: X-ray crystallography X-ray crystallography NMR spectroscopy NMR spectroscopy Homology modelling Homology modelling

Molecular Simulation Where do we get the structures from? Where do we get the structures from? Databases Databases Brookhaven protein data base Brookhaven protein data base Or homology models Or homology models

Molecular Simulation Homology modelling: Homology modelling:

Molecular Simulation Molecular Mechanics: Molecular Mechanics: The Potential energy surface (PES): The Potential energy surface (PES): Born-Oppenheimer approx. allows us to separate electronic and nuclear motion Born-Oppenheimer approx. allows us to separate electronic and nuclear motion when nuclei move, the electrons re-adjust quickly when nuclei move, the electrons re-adjust quickly energy of molecule is a function of the positions of the nuclei 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 potential energy surface describes energy of a molecule in terms of its structure

Molecular Simulation

Structure Structure determined from the potential energy surface determined from the potential energy surface minimum corresponds to an equilibrium structure minimum corresponds to an equilibrium structure first order saddle point corresponds to a transition state for a reaction 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 a reaction path is the steepest descent path connecting a transition state to minima Dynamics Dynamics molecules move on the potential energy surface molecules move on the potential energy surface dynamics can be treated classically or quantum mechanically dynamics can be treated classically or quantum mechanically small amplitude motions - normal modes of vibration small amplitude motions - normal modes of vibration large amplitude motions - trajectories, wave packets, reactions large amplitude motions - trajectories, wave packets, reactions statistical mechanics to connect microscopic to macroscopic statistical mechanics to connect microscopic to macroscopic

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

Molecular Simulation Bond Stretching and valence angle bending Bond Stretching and valence angle bending

Molecular Simulations Torsions Torsions

Molecular Simulation Interaction of 2 point charges Interaction of 2 point charges

Molecular Simulation Van der Waals Interactions Van der Waals Interactions

Molecular Simulation Force Field Energies Force Field Energies Geometry Optimisation Geometry Optimisation Thermodynamics Thermodynamics

Molecular Simulation Modern Force Fields Modern Force Fields CHARMMBiomolecules CHARMMBiomolecules CHARMmBio and org. molecules CHARMmBio and org. molecules CFF/CVFForg. and bio molecules CFF/CVFForg. and bio molecules GROMOSBiomolecules GROMOSBiomolecules MM2organics MM2organics MM3org. and bio molecules MM3org. and bio molecules OPLSall-atom and united atom version OPLSall-atom and united atom version SYBYL/TRIPOSorg. and bio molecules SYBYL/TRIPOSorg. and bio molecules