Improved Computation of Protein–Protein Relative Binding Energies with the Nwat-MMGBSA Method

A MMGBSA variant
(here referred to as Nwat-MMGBSA), based on the
inclusion of a certain number of explicit water molecules (Nwat) during
the calculations, has been tested on a set of 20 protein–protein
complexes, using the correlation between predicted and experimental
binding energy as the evaluation metric. Besides the Nwat parameter,
the effect of the force field, the molecular dynamics simulation length,
and the implicit solvent model used in the MMGBSA analysis have been
also evaluated. We found that considering 30 interfacial water molecules
improved the correlation between predicted and experimental binding
energies by up to 30%, compared to the standard approach. Moreover,
the correlation resulted in being rather sensitive to the force field
and, to a minor extent, to the implicit solvent model and to the length
of the MD simulation.