Comparison of free-energy methods using a tripeptide-water model system

Bibliographische Detailangaben
Veröffentlicht in:	Journal of computational chemistry. - 1984. - 39(2018), 26 vom: 05. Okt., Seite 2226-2242
1. Verfasser:	Maurer, Manuela (VerfasserIn)
Weitere Verfasser:	Hansen, Niels, Oostenbrink, Chris
Format:	Online-Aufsatz
Sprache:	English
Veröffentlicht:	2018
Zugriff auf das übergeordnete Werk:	Journal of computational chemistry
Schlagworte:	Comparative Study Journal Article Research Support, Non-U.S. Gov't GROMOS active-site water free-energy calculations molecular dynamics simulations Oligopeptides Water 059QF0KO0R

Beschreibung
Zusammenfassung:	© 2018 The Authors. Journal of Computational Chemistry published by Wiley Periodicals, Inc. We investigate the ability of several free-energy calculation methods to combine two alchemical changes. We use Bennett acceptance ratio (BAR), thermodynamic integration (TI), extended TI (X-TI), and enveloping distribution sampling (EDS) to perturb a water molecule, which is restrained to an amino acid that is also being perturbed. In addition to these pairwise methods, we present two two-dimensional approaches, EDS-TI and two-dimensional TI (2D-TI). We compare feasibility, efficiency and usability of these methods in regard to our simple model system, which mimics the displacement of a water molecule in the active site of a protein on residue mutation. The correct treatment of structural water has been shown to greatly aid binding affinity calculations in some cases that remained elusive otherwise. This is of broad interest in, for example, drug design, and we conclude that thus far, the pairwise method BAR and also the newer X-TI remain the most suitable methods to treat this problem as long as few end states are involved. © 2018 Wiley Periodicals, Inc
Beschreibung:	Date Completed 18.09.2019 Date Revised 14.02.2024 published: Print-Electronic Citation Status MEDLINE
ISSN:	1096-987X
DOI:	10.1002/jcc.25537