Calculation of protein-ligand binding free energy by using a polarizable potential.

ABSTRACT: The binding of charged ligands benzamidine and diazamidine to trypsin was investigated by using a polarizable potential energy function and explicit-water molecular dynamics simulations. The binding free energies were computed from the difference between the free energies of decoupling the ligand from water and protein environments. Both the absolute and the relative free energies from the perturbation simulations agree with experimental measurements to within 0.5 kcal.mol(-1). Comparison of free-energy components sampled from different thermodynamic paths indicates that electrostatics is the main driving force behind benzamidine recognition of trypsin. The contribution of electronic polarization to binding appears to be crucial. By computing the free-energy contribution caused by the pola

SUBMITTER: Jiao D 

PROVIDER: S-EPMC2359813 | biostudies-literature | 2008 Apr

REPOSITORIES: biostudies-literature