title: Improved Computation of Protein-Protein Relative Binding Energies with the Nwat-MMGBSA Method.
abstract: 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.
authors: Dipartimento di Scienze Farmaceutiche - Sezione di Chimica Generale e Organica "Alessandro Marchesini", Università degli Studi di Milano , Via Venezian, 21, 20133 Milano, Italy.
authors: Irene
authors: I
authors: Maffucci
authors: Dipartimento di Scienze Farmaceutiche - Sezione di Chimica Generale e Organica "Alessandro Marchesini", Università degli Studi di Milano , Via Venezian, 21, 20133 Milano, Italy.
authors: Alessandro
authors: A
authors: Contini
mesh_terms: D015195:Drug Design; D006860:Hydrogen Bonding; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D011487:Protein Conformation; D025941:Protein Interaction Mapping; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D013816:Thermodynamics; D014867:Water / Q000737:chemistry
chemical_list: D011506:Proteins; D014867:Water