Effect of polarization on HIV-1protease and fluoro-substituted inhibitors binding energies by large scale molecular dynamics simulations.

ABSTRACT: Molecular dynamics simulations in explicit water are carried out to study the binding of six inhibitors to HIV-1 protease (PR) for up to 700 ns using the standard AMBER force field and polarized protein-specific charge (PPC). PPC is derived from quantum mechanical calculation for protein in solution and therefore it includes electronic polarization effect. Our results show that in all six systems, the bridging water W301 drifts away from the binding pocket in AMBER simulation. However, it is very stable in all six complexes systems using PPC. Especially, intra-protease, protease-inhibitor hydrogen bonds are dynamic stabilized in MD simulation. The computed binding free energies of six complexes have a significantly linear correlation with those experiment values and the correlation coeffic

SUBMITTER: Duan LL 

PROVIDER: S-EPMC5290483 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature