Wan, S;
Tresadern, G;
Pérez‐Benito, L;
Vlijmen, H;
Coveney, PV;
(2020)
Accuracy and Precision of Alchemical Relative Free Energy Predictions with and without Replica‐Exchange.
Advanced Theory and Simulations
, 3
(1)
, Article 1900195. 10.1002/adts.201900195.
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Abstract
A systematic and statistically robust protocol is applied for the evaluation of free energy calculations with and without replica‐exchange. The protocol is based on ensemble averaging to generate accurate assessments of the uncertainties in the predictions. Comparison is made between FEP+ and TIES—free energy perturbation and thermodynamic integration with enhanced sampling—the latter with and without the so‐called “enhanced sampling” based on replica‐exchange protocols. Standard TIES performs best for a reference set of targets and compounds; no benefits accrue from replica‐exchange methods. Evaluation of FEP+ and TIES with REST—replica‐exchange with solute tempering—reveals a systematic and significant underestimation of free energy differences in FEP+, which becomes increasingly large for long duration simulations, is confirmed by extensive analysis of previous publications, and raises a number of questions pertaining to the accuracy of the predictions with the REST technique not hitherto discussed.
| Type: | Article |
|---|---|
| Title: | Accuracy and Precision of Alchemical Relative Free Energy Predictions with and without Replica‐Exchange |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/adts.201900195 |
| Publisher version: | https://doi.org/10.1002/adts.201900195 |
| Language: | English |
| Additional information: | Copyright © 2019 The Authors. Published by WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim. This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | binding free energies, FEP+, replica‐exchange, thermodynamic integration with enhanced sampling |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Chemistry |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10087686 |
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