BIOINFORMATICS Simulation
Overview: Electrostatics + Basic Forces
Overview: Methods for the Generation and Analysis of Macromolecular Simulations
Electric potential, a quick review
Maxwell's Equations
Multipole Expansion
Gauss’ Law: Electrostatics
Dipole Derivation
Polariz-ation
Dielectric const.
Polarity vs. Polarizability
VDW Forces: Start by Deriving Dipole-Dipole Energy
Average Dipole-Dipole Interaction Energy
Dipole-induced dipole Energy
VDW Foces: Induced dipole-induced dipole
Packing ~ VDW force
Close-packing is Default
Small Packing Changes Significant
Different Sets of Radii
Molecular Mechanics: Simple electrostatics
H-bonds subsumed by electrostatic interactions
Bond Length Springs
Bond angle, More Springs
Torsion angle
Potential Functions
Sum up to get total energy
Energy Scale of Interactions
Elaboration on the Basic Protein Model
Goal: Model Proteins and Nucleic Acids as Real Physical Molecules
Ways to Move Protein on its Energy Surface
Steepest Descent Minimization
Multi-dimensional Minimization
Other Minimization Methods
Adiabatic mapping
Molecular Dynamics
Molecular Dynamics (cont)
Phase Space Walk
Example Phase Space Walk
Monte Carlo
Monte Carlo (cont)
MC vs/+ MD
Moving Molecules Rigidly
Typical Systems: Water v. Argon
Typical Systems: DNA + Water
Typical Systems: Protein + Water
Practical Aspects: simulation cycle I
Practical Aspects: simulation cycle II
Sample Protein Parameters (toph19.pro)
Sample Protein Parameters (toph19.pro)
Sample Protein Parameters (param19.pro)
Sample Protein Parameters (param19.pro)
Sample Protein Parameters (param19.pro)
Sample Protein Parameters (param19.pro)
Periodic Boundary Conditions
Average over simulation
Timescales
D & RMS
Number Density
Number Density (cont)
Major Protein Simulation Packages
Molecular Biophysics & Biochemistry 400a/700a (Advanced Biochemistry)
The Handouts
The Handouts II
Outline
Practical Aspects: simulation cycle I
Practical Aspects: simulation cycle II
Major Protein Simulation Packages
Moving Molecules Rigidly
Simulation, Part II: Analysis: What can be Calculated from Simulation?
Average over simulation
Energy and Entropy
Application of Simulation: Thermodynamic Cycles
Number Density
Number Density (cont)
Measurement of Dynamic Quantities I
Measurement of Dynamic Quantities II
D & RMS
Observed RMS values
Other Things to Calculate
Monitor Stability of Specific Hydrogen Bonds
Energy Landscapes and Barriers Traversed in a Simulation
Timescales
Electrostatics Revisited: the Poisson-Boltzmann Equation
Poisson-Boltzmann equation
Simplifications of the Poisson-Boltzmann equation
Protein on a Grid
Demand Consistency on the Grid
Adding a Dielectric Boundary into the Model
Electrostatic Potential of Thrombin
Increasing Ionic Strength
Increasing Dielectric
pKa shifts
pKa continued I
pKa continued II
Water Simulation and Hydrophobicity
Simulating Liquid Water
Periodic Boundary Conditions
Tetrahedral Geometry of Water
HydrophobicityArises Naturally in Simulation
Different Behavior of Water around Hydrophobic and Hydrophilic Solutes
Consequences of Hydrophobic Hydration and “Clathrate” Formation
Ways of Rationalizing Packing
PPT Slide
PPT Slide
Water around Hydrophobic Groups on protein surface is more Compressible
Interaction Between Water and the Protein Surface
Simple Two Helix System
Second Solvent Shell: Water v LJ Liquid
Water vs. Ar (Helical Project-ions)
Hydration Surface
Water Participates in Protein Unfolding
Simplified Simulation
Simplification
Simplified Protein: Lattice Models
Off-lattice Discrete State Models
How Well Do Lattice Structures Match Real Protein Structure?
How well does the off-lattice model fit?
Simplified Solvent
Review -- Basic Forces
Review -- Simulation
Demos
References
References 2
References
References 2