Flexible Fitting of Small Molecules into Electron Microscopy Maps Using Molecular Dynamics Simulations with Neural Network Potentials.

ABSTRACT: Despite significant advances in resolution, the potential for cryo-electron microscopy (EM) to be used in determining the structures of protein-drug complexes remains unrealized. Determination of accurate structures and coordination of bound ligands necessitates simultaneous fitting of the models into the density envelopes, exhaustive sampling of the ligand geometries, and, most importantly, concomitant rearrangements in the side chains to optimize the binding energy changes. In this article, we present a flexible-fitting pipeline where molecular dynamics flexible fitting (MDFF) is used to refine structures of protein-ligand complexes from 3 to 5 Å electron density data. Enhanced sampling is employed to explore the binding pocket rearrangements. To provide a model that can accurately descr

SUBMITTER: Vant JW 

PROVIDER: S-EPMC7311632 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature