Paper Info
Title
Comparison Of Free-Energy Methods Using A Tripeptide-Water Model System
Abstract
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. (c) 2018 Wiley Periodicals, Inc.
Year
DOI
Venue
2018
10.1002/jcc.25537
JOURNAL OF COMPUTATIONAL CHEMISTRY
Keywords
DocType
Volume
free-energy calculations, molecular dynamics simulations, active-site water, GROMOS
Journal
39
Issue
ISSN
Citations 
26
0192-8651
0
PageRank 
References 
Authors
0.34
0
3
Name
Order
Citations
PageRank
Manuela Maurer100.68
Niels Hansen200.68
Chris Oostenbrink329738.41