Oversampling Free Energy Perturbation Simulation in Determination of the Ligand-Binding Free Energy
© 2019 Wiley Periodicals, Inc.
| Veröffentlicht in: | Journal of computational chemistry. - 1984. - 41(2020), 7 vom: 15. März, Seite 611-618 |
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| 1. Verfasser: | |
| Weitere Verfasser: | , , , , |
| Format: | Online-Aufsatz |
| Sprache: | English |
| Veröffentlicht: |
2020
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| Zugriff auf das übergeordnete Werk: | Journal of computational chemistry |
| Schlagworte: | Journal Article Research Support, Non-U.S. Gov't FEP REP binding free energy perturbation replica exchange molecular dynamics |
| Zusammenfassung: | © 2019 Wiley Periodicals, Inc. Determination of the ligand-binding affinity is an extremely interesting problem. Normally, the free energy perturbation (FEP) method provides an appropriate result. However, it is of great interest to improve the accuracy and precision of this method. In this context, temperature replica exchange molecular dynamics implementation of the FEP computational approach, which we call replica exchange free energy perturbation (REP) was proposed. In particular, during REP simulations, the system can easily escape from being trapped in local minima by exchanging configurations with high temperatures, resulting in significant improvement in the accuracy and precision of protein-ligand binding affinity calculations. The distribution of the decoupling free energy was enlarged, and its mean values were decreased. This results in changes in the magnitude of the calculated binding free energies as well as in alteration in the binding mechanism. Moreover, the REP correlation coefficient with respect to experiment ( RREP = 0.85 ± 0.15) is significantly boosted in comparison with the FEP one ( RFEP = 0.64 ± 0.30). Furthermore, the root-mean-square error (RMSE) of REP is also smaller than FEP, RMSEREP = 4.28 ± 0.69 versus RMSEFEP = 5.80 ± 1.11 kcal/mol, respectively. © 2019 Wiley Periodicals, Inc |
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| Beschreibung: | Date Completed 30.09.2020 Date Revised 01.10.2020 published: Print-Electronic Citation Status PubMed-not-MEDLINE |
| ISSN: | 1096-987X |
| DOI: | 10.1002/jcc.26130 |