Trypsin-ligand binding free energies from explicit and implicit solvent simulations with polarizable potential.

ABSTRACT: We have calculated the binding free energies of a series of benzamidine-like inhibitors to trypsin with a polarizable force field using both explicit and implicit solvent approaches. Free energy perturbation has been performed for the ligands in bulk water and in protein complex with molecular dynamics simulations. The binding free energies calculated from explicit solvent simulations are well within the accuracy of experimental measurement and the direction of change is predicted correctly in all cases. We analyzed the molecular dipole moments of the ligands in gas, water and protein environments. Neither binding affinity nor ligand solvation free energy in bulk water shows much dependence on the molecular dipole moments of the ligands. Substitution of the aromatic or the charged group in

SUBMITTER: Jiao D 

PROVIDER: S-EPMC2752704 | biostudies-literature | 2009 Aug

REPOSITORIES: biostudies-literature