Improving Prediction Accuracy of Binding Free Energies and Poses of HIV Integrase Complexes Using the Binding Energy Distribution Analysis Method with Flattening Potentials.

ABSTRACT: To accelerate conformation sampling of slow dynamics from receptor or ligand, we introduced flattening potentials on selected bonded and nonbonded intramolecular interactions to the binding energy distribution analysis method (BEDAM) for calculating absolute binding free energies of protein-ligand complexes using an implicit solvent model and implemented flattening BEDAM using the asynchronous replica exchange (AsyncRE) framework for performing large scale replica exchange molecular dynamics (REMD) simulations. The advantage of using the flattening feature to reduce high energy barriers was exhibited first by the p-xylene-T4 lysozyme complex, where the intramolecular interactions of a protein side chain on the binding site were flattened to accelerate the conformational transition of the s

SUBMITTER: Xia J 

PROVIDER: S-EPMC6287956 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature