Chemical Physics Letters, Vol.676, 12-17, 2017
Determination of the absolute binding free energies of HIV-1 protease inhibitors using non-equilibrium molecular dynamics simulations
The absolute binding free energy of an inhibitor to HIV-1 Protease (PR) was determined throughout evaluation of the non-bonded interaction energy difference between the two bound and unbound states of the inhibitor and surrounding molecules by the fast pulling of ligand (FPL) process using non-equilibrium molecular dynamics (NEMD) simulations. The calculated free energy difference terms help clarifying the nature of the binding. Theoretical binding affinities are in good correlation with experimental data, with R = 0.89. The paradigm used is able to rank two inhibitors having the maximum difference of similar to 1.5 kcal/mol in absolute binding free energies. (C) 2017 Elsevier B.V. All rights reserved.
Keywords:Fast pulling of ligand approach;HIV-1 PR;NEMD simulations;Absolute binding affinity;Interaction energy;Pulling work