Fast and accurate determination of the relative binding affinities of small compounds to HIV-1 protease using non-equilibrium work
© 2016 Wiley Periodicals, Inc.
| Veröffentlicht in: | Journal of computational chemistry. - 1984. - 37(2016), 31 vom: 05. Dez., Seite 2734-2742 |
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| Format: | Online-Aufsatz |
| Sprache: | English |
| Veröffentlicht: |
2016
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| Zugriff auf das übergeordnete Werk: | Journal of computational chemistry |
| Schlagworte: | Journal Article Research Support, Non-U.S. Gov't HIV-1 protease fast pulling ligand nature of binding non-equilibrium molecular dynamics non-equilibrium work relative binding affinity rupture force steered molecular dynamics mehr... |
| Zusammenfassung: | © 2016 Wiley Periodicals, Inc. The fast pulling ligand (FPL) out of binding cavity using non-equilibrium molecular dynamics (MD) simulations was demonstrated to be a rapid, accurate and low CPU demand method for the determination of the relative binding affinities of a large number of HIV-1 protease (PR) inhibitors. In this approach, the ligand is pulled out of the binding cavity of the protein using external harmonic forces, and the work of pulling force corresponds to the relative binding affinity of HIV-1 PR inhibitor. The correlation coefficient between the pulling work and the experimental binding free energy of R=-0.95 shows that FPL results are in good agreement with experiment. It is thus easier to rank the binding affinities of HIV-1 PR inhibitors, that have similar binding affinities because the mean error bar of pulling work amounts to δW=7%. The nature of binding is discovered using the FPL approach. © 2016 Wiley Periodicals, Inc |
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| Beschreibung: | Date Completed 24.07.2018 Date Revised 24.07.2018 published: Print-Electronic Citation Status MEDLINE |
| ISSN: | 1096-987X |
| DOI: | 10.1002/jcc.24502 |