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.

Improved Computation of Protein–Protein Relative Binding Energies with the Nwat-MMGBSA Method / I. Maffucci, A. Contini. - In: JOURNAL OF CHEMICAL INFORMATION AND MODELING. - ISSN 1549-9596. - 56:9(2016 Sep), pp. 1692-1704. [10.1021/acs.jcim.6b00196]

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

I. Maffucci
Primo
;
A. Contini
2016-09

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.
protein-protein interaction; molecular dynamics; MMGBSA; MMPBSA; water; force field; interface; implicit solvent model
Settore CHIM/06 - Chimica Organica
8-ago-2016
Article (author)
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/429456
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