PyFepRestr: Plugin to PyMOL Molecular Graphics System for Calculating the Free Energy of Ligand‒Receptor Binding

Abstract

The calculations of the free energy of ligand binding with a receptor (most often, protein) are widely used in the rational design of new bioactive compounds. The gold standard of such calculations is the equilibrium methods based on molecular dynamics and the “alchemical” transformations, including the thermodynamic integration and Bennett method. Technically, these methods call for introduction of additional restraints on the mutual arrangement of atoms in the ligand–receptor system. A plugin to the PyMOL molecular graphics system has been developed to facilitate the introduction of required restraints and analytical calculation of correction when computing the free energy of ligand‒receptor (protein) binding.