Sensitivity in Binding Free Energies Due to Protein Reorganization.

ABSTRACT: Tremendous recent improvements in computer hardware, coupled with advances in sampling techniques and force fields, are now allowing protein-ligand binding free energy calculations to be routinely used to aid pharmaceutical drug discovery projects. However, despite these recent innovations, there are still needs for further improvement in sampling algorithms to more adequately sample protein motion relevant to protein-ligand binding. Here, we report our work identifying and studying such clear and remaining needs in the apolar cavity of T4 lysozyme L99A. In this study, we model recent experimental results that show the progressive opening of the binding pocket in response to a series of homologous ligands.1 Even while using enhanced sampling techniques, we demonstrate that the predicted re

SUBMITTER: Lim NM 

PROVIDER: S-EPMC5021633 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature