Published July 27, 2021 | Version v1
Journal article Open

Virtual Double-System Single-Box for Absolute Dissociation Free Energy Calculations in GROMACS

  • 1. Università degli Studi di Firenze
  • 2. University of Geneva, CH

Description

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 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 (3CLpro) of SARS-CoV-2.

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