Pre-Exascale Computing of Protein-Ligand Binding Free Energies with Open Source Software for Drug Design.


Journal

Journal of chemical information and modeling
ISSN: 1549-960X
Titre abrégé: J Chem Inf Model
Pays: United States
ID NLM: 101230060

Informations de publication

Date de publication:
14 03 2022
Historique:
pubmed: 23 2 2022
medline: 25 3 2022
entrez: 22 2 2022
Statut: ppublish

Résumé

Nowadays, drug design projects benefit from highly accurate protein-ligand binding free energy predictions based on molecular dynamics simulations. While such calculations have been computationally expensive in the past, we now demonstrate that workflows built on open source software packages can efficiently leverage pre-exascale computing resources to screen hundreds of compounds in a matter of days. We report our results of free energy calculations on a large set of pharmaceutically relevant targets assembled to reflect industrial drug discovery projects.

Identifiants

pubmed: 35191702
doi: 10.1021/acs.jcim.1c01445
pmc: PMC8924919
doi:

Substances chimiques

Ligands 0

Types de publication

Letter Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1172-1177

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Auteurs

Vytautas Gapsys (V)

Computational Biomolecular Dynamics Group, Max-Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany.

David F Hahn (DF)

Computational Chemistry, Janssen Research and Development, Janssen Pharmaceutica N. V., Turnhoutseweg 30, 2340 Beerse, Belgium.

Gary Tresadern (G)

Computational Chemistry, Janssen Research and Development, Janssen Pharmaceutica N. V., Turnhoutseweg 30, 2340 Beerse, Belgium.

David L Mobley (DL)

Department of Pharmaceutical Sciences, University of California, Irvine, California 92697, United States.

Markus Rampp (M)

Max-Planck Computing and Data Facility, Giessenbachstrasse 2, 85748 Garching, Germany.

Bert L de Groot (BL)

Computational Biomolecular Dynamics Group, Max-Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany.

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Classifications MeSH