ExplicitsolventmodelsIncludes individual solvent molecules;If solution is dilute, how to construct its solvation shell?-How many shells? Geometry of solvent molecules?How todeal withthe boundary?- Require 100-1000 of solvent molecules surrounding thesolute;Calculatethefreeenergyof solvationbysimulating solutesolvent interactions;Verylengthycalculations;Requires an empirical interaction potential between thesolvent and solute, and between the solvent molecules;
Explicit solvent models • Includes individual solvent molecules; • If solution is dilute, how to construct its solvation shell? – How many shells? Geometry of solvent molecules? How to deal with the boundary? – Require 100-1000 of solvent molecules surrounding the solute; • Calculate the free energy of solvation by simulating solutesolvent interactions; • Very lengthy calculations; • Requires an empirical interaction potential between the solvent and solute, and between the solvent molecules; 7
QM/MMQuantum mechanical treatment of the solute andmolecular mechanical treatment of the solvent;-Replacesthesolventmoleculeswithpartialcharges;- e. g., TIP3P uses S+ = 0.417 and S- = -0.834;S+H-O18+HRestricted to research groups that specialize in suchthings;: GAMESS-US (effective fragment potential, EFP);Good“blackbox"implementationsare notgenerallyavailable;8
QM/MM • Quantum mechanical treatment of the solute and molecular mechanical treatment of the solvent; – Replaces the solvent molecules with partial charges; – e. g., TIP3P uses δ+ = 0.417 and δ– = –0.834; 8 • Restricted to research groups that specialize in such things; • GAMESS-US (effective fragment potential, EFP); • Good “black box” implementations are not generally available;
MonteCarlosimulationsBox containing a solute and solvent molecules(periodic boundary conditions); Random moves of molecules;If energy goes down, accept the move;If energy goes up, accept according to Boltzmannprobability; MC calculations can be used to compute free energydifferences, radial distribution functions, etc.; Cannot be used to compute time dependentproperties such as diffusion coefficients, viscosity,etc.9
Monte Carlo simulations • Box containing a solute and solvent molecules (periodic boundary conditions); • Random moves of molecules; • If energy goes down, accept the move; • If energy goes up, accept according to Boltzmann probability; • MC calculations can be used to compute free energy differences, radial distribution functions, etc.; • Cannot be used to compute time dependent properties such as diffusion coefficients, viscosity, etc. 9
MolecularDynamicssimulations· Use classical equations to simulate themotion of the molecules for a suitablylong time (100's ps to ns);Requires energies and gradients of thepotential; In addition to free energies, can be usedto compute time dependent propertiestransport properties, correlation functions,etc.;10
Molecular Dynamics simulations • Use classical equations to simulate the motion of the molecules for a suitably long time (100’s ps to ns); • Requires energies and gradients of the potential; • In addition to free energies, can be used to compute time dependent properties transport properties, correlation functions, etc.; 10