Computational design of a substrate specificity mutant of a protein.

N Honda, Y Komeiji, M Uebayasi, I Yamato

Index: Proteins 26(4) , 459-64, (1996)

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Abstract

The wild-type trp repressor of E. coli bound 5-methoxytryptophan, a Trp analogue, less tightly than Trp. A mutant repressor (Val58-->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.