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The F130L mutation in streptavidin reduces its binding affinity to biotin through electronic polarization effect
Author(s) -
Zeng Juan,
Jia Xiangyu,
Zhang John Z. H.,
Mei Ye
Publication year - 2013
Publication title -
journal of computational chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.907
H-Index - 188
eISSN - 1096-987X
pISSN - 0192-8651
DOI - 10.1002/jcc.23421
Subject(s) - streptavidin , chemistry , binding energy , biotin , affinities , mutant , binding site , biotinylation , point mutation , biophysics , stereochemistry , atomic physics , biochemistry , physics , biology , gene
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. © 2013 Wiley Periodicals, Inc.