Protein-ligand binding with the coarse-grained Martini model.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
24 07 2020
24 07 2020
Historique:
received:
29
08
2019
accepted:
29
06
2020
entrez:
26
7
2020
pubmed:
28
7
2020
medline:
9
9
2020
Statut:
epublish
Résumé
The detailed understanding of the binding of small molecules to proteins is the key for the development of novel drugs or to increase the acceptance of substrates by enzymes. Nowadays, computer-aided design of protein-ligand binding is an important tool to accomplish this task. Current approaches typically rely on high-throughput docking essays or computationally expensive atomistic molecular dynamics simulations. Here, we present an approach to use the recently re-parametrized coarse-grained Martini model to perform unbiased millisecond sampling of protein-ligand interactions of small drug-like molecules. Remarkably, we achieve high accuracy without the need of any a priori knowledge of binding pockets or pathways. Our approach is applied to a range of systems from the well-characterized T4 lysozyme over members of the GPCR family and nuclear receptors to a variety of enzymes. The presented results open the way to high-throughput screening of ligand libraries or protein mutations using the coarse-grained Martini model.
Identifiants
pubmed: 32709852
doi: 10.1038/s41467-020-17437-5
pii: 10.1038/s41467-020-17437-5
pmc: PMC7382508
doi:
Substances chimiques
Ligands
0
Proteins
0
Muramidase
EC 3.2.1.17
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3714Références
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