TY  - JOUR
AU  - Sweeney, Aaron
AU  - Mulvaney, Thomas
AU  - Maiorca, Mauro
AU  - Topf, Maya
TI  - ChemEM: Flexible Docking of Small Molecules in Cryo-EM Structures
JO  - Journal of medicinal chemistry
VL  - 67
IS  - 1
SN  - 0022-2623
CY  - Washington, DC
PB  - ACS
M1  - PUBDB-2024-05632
SP  - 199-212
PY  - 2023
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:38157562
UR  - <Go to ISI:>//WOS:001141756000001
DO  - DOI:10.1021/acs.jmedchem.3c01134
UR  - https://bib-pubdb1.desy.de/record/613805
ER  -