The F130L mutation in streptavidin reduces its binding affinity to biotin through electronic polarization effect
Copyright © 2013 Wiley Periodicals, Inc.
| Veröffentlicht in: | Journal of computational chemistry. - 1984. - 34(2013), 31 vom: 05. Dez., Seite 2677-86 |
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| Format: | Online-Aufsatz |
| Sprache: | English |
| Veröffentlicht: |
2013
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| Zugriff auf das übergeordnete Werk: | Journal of computational chemistry |
| Schlagworte: | Journal Article Research Support, Non-U.S. Gov't binding free energy biotin mutation polarization streptavidin Biotin 6SO6U10H04 Streptavidin |
| Zusammenfassung: | Copyright © 2013 Wiley Periodicals, Inc. Recently, Baugh et al. discovered that a distal point mutation (F130L) in streptavidin causes no distinct variation to the structure of the binding pocket but a 1000-fold reduction in biotin binding affinity. In this work, we carry out molecular dynamics simulations and apply an end-state free energy method to calculate the binding free energies of biotin to wild type streptavidin and its F130L mutant. The absolute binding affinities based on AMBER charge are repulsive, and the mutation induced binding loss is underestimated. When using the polarized protein-specific charge, the absolute binding affinities are significantly enhanced. In particular, both the absolute and relative binding affinities are in line with the experimental measurements. Further investigation indicates that polarization effect is indispensable in both the generation of structural ensembles and the calculation of interaction energies. This work verifies Baugh's conjecture that electrostatic polarization effect plays an essential role in modulating the binding affinity of biotin to the streptavidin through F130L mutation |
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| Beschreibung: | Date Completed 12.05.2014 Date Revised 24.10.2013 published: Print-Electronic Citation Status MEDLINE |
| ISSN: | 1096-987X |
| DOI: | 10.1002/jcc.23421 |