Automatic and accurate ligand structure determination guided by cryo-electron microscopy maps.

ABSTRACT: Advances in cryo-electron microscopy (cryoEM) and deep-learning guided protein structure prediction have expedited structural studies of protein complexes. However, methods for accurately determining ligand conformations are lacking. In this manuscript, we develop EMERALD, a tool for automatically determining ligand structures guided by medium-resolution cryoEM density. We show this method is robust at predicting ligands along with surrounding side chains in maps as low as 4.5 Å local resolution. Combining this with a measure of placement confidence and running on all protein/ligand structures in the EMDB, we show that 57% of ligands replicate the deposited model, 16% confidently find alternate conformations, 22% have ambiguous density where multiple conformations might be present, and 5%

SUBMITTER: Muenks A 

PROVIDER: S-EPMC9976687 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature