Virtual Double-System Single-Box for Absolute Dissociation Free Energy Calculations in GROMACS.
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:
22 11 2021
22 11 2021
Historique:
pubmed:
2
11
2021
medline:
25
11
2021
entrez:
1
11
2021
Statut:
ppublish
Résumé
We describe a step-by-step protocol for the computation of absolute dissociation free energy with GROMACS code and PLUMED library, which exploits a combination of advanced sampling techniques and nonequilibrium alchemical methodologies. The computational protocol has been automated through an open source Python middleware (HPC_Drug) which allows one to set up the GROMACS/PLUMED input files for execution on high performing computing facilities. The proposed protocol, by exploiting its inherent parallelism and the power of the GROMACS code on graphical processing units, has the potential to afford accurate and precise estimates of the dissociation constants in drug-receptor systems described at the atomistic level. The procedure has been applied to the calculation of the absolute dissociation free energy of PF-07321332, an oral antiviral proposed by Pfizer, with the main protease (3CL
Identifiants
pubmed: 34723516
doi: 10.1021/acs.jcim.1c00909
pmc: PMC8611716
doi:
Substances chimiques
Antiviral Agents
0
Lactams
0
Nitriles
0
nirmatrelvir
7R9A5P7H32
Proline
9DLQ4CIU6V
Leucine
GMW67QNF9C
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5320-5326Références
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