Open AccessVirtual Double-System Single-Box for Absolute Dissociation Free Energy Calculations in GROMACS
Author(s) -
Marina Macchiagodena,
Maurice Karrenbrock,
Marco Pagliai,
Piero Procacci
Publication year - 2021
Publication title -
journal of chemical information and modeling
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 160
eISSN - 1549-960X
pISSN - 1549-9596
DOI - 10.1021/acs.jcim.1c00909
Subject(s) - computer science , computational science , parallel computing , bond dissociation energy , python (programming language) , computation , rendering (computer graphics) , dissociation (chemistry) , chemistry , algorithm , operating system , computer graphics (images)
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 pro ) of SARS-CoV-2.