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Computational design of a substrate specificity mutant of a protein
Author(s) -
Honda Nobuo,
Komeiji Yuto,
Uebayasi Masami,
Yamato Ichiro
Publication year - 1996
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/(sici)1097-0134(199612)26:4<459::aid-prot6>3.0.co;2-6
Subject(s) - mutant , repressor , chemistry , decomposition , substrate specificity , substrate (aquarium) , protein design , biophysics , biochemistry , enzyme , protein structure , biology , gene , transcription factor , ecology , organic chemistry
The wild‐type trp repressor of E. coli bound 5‐methoxytryptophan, a Trp analogue, less tightly than Trp. A mutant repressor (Val 58 →Ala) that should bind 5‐methoxytryptophan preferentially to Trp was computationally designed by free‐energy calculations accompanied by free‐energy decomposition. The designed mutant was demonstrated by experiments to bind 5‐methoxytryptophan more tightly than Trp, consistent with the computational prediction. This success indicates the usefulness of free energy decomposition in protein design. Proteins 26:459–464 © 1996 Wiley‐Liss, Inc.