%0 Journal Article
%A Sweeney, Aaron
%A Mulvaney, Thomas
%A Maiorca, Mauro
%A Topf, Maya
%T ChemEM: Flexible Docking of Small Molecules in Cryo-EM Structures
%J Journal of medicinal chemistry
%V 67
%N 1
%@ 0022-2623
%C Washington, DC
%I ACS
%M PUBDB-2024-05632
%P 199-212
%D 2023
%X Cryo-electron microscopy (cryo-EM), through resolution advancements, has become pivotal in structure-based drug discovery. However, most cryo-EM structures are solved at 3–4 Å resolution, posing challenges for small-molecule docking and structure-based virtual screening due to issues in the precise positioning of ligands and the surrounding side chains. We present ChemEM, a software package that employs cryo-EM data for the accurate docking of one or multiple ligands in a protein-binding site. Validated against a highly curated benchmark of high- and medium-resolution cryo-EM structures and the corresponding high-resolution controls, ChemEM displayed impressive performance, accurately placing ligands in all but one case, often surpassing cryo-EM PDB-deposited solutions. Even without including the cryo-EM density, the ChemEM scoring function outperformed the well-established AutoDock Vina score. Using ChemEM, we illustrate that valuable information can be extracted from maps at medium resolution and underline the utility of cryo-EM structures for drug discovery.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:38157562
%U <Go to ISI:>//WOS:001141756000001
%R 10.1021/acs.jmedchem.3c01134
%U https://bib-pubdb1.desy.de/record/613805