Assessment of a Single Decoupling Alchemical Approach for the Calculation of the Absolute Binding Free Energies of Protein-Peptide Complexes.

ABSTRACT: The computational modeling of peptide inhibitors to target protein-protein binding interfaces is growing in interest as these are often too large, too shallow, and too feature-less for conventional small molecule compounds. Here, we present a rare successful application of an alchemical binding free energy method for the calculation of converged absolute binding free energies of a series of protein-peptide complexes. Specifically, we report the binding free energies of a series of cyclic peptides derived from the LEDGF/p75 protein to the integrase receptor of the HIV1 virus. The simulations recapitulate the effect of mutations relative to the wild-type binding motif of LEDGF/p75, providing structural, energetic and dynamical interpretations of the observed trends. The equilibration and con

SUBMITTER: Kilburg D 

PROVIDER: S-EPMC5852065 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature