title: Computational design of a substrate specificity mutant of a protein.
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.
authors.affiliation: Department of Biological Science and Technology, Science University of Tokyo, Chiba, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Honda
authors.forename: Y
authors.initials: Y
authors.lastname: Komeiji
authors.forename: M
authors.initials: M
authors.lastname: Uebayasi
authors.forename: I
authors.initials: I
authors.lastname: Yamato
mesh_terms: D001426:Bacterial Proteins; D008956:Models, Chemical; D016296:Mutagenesis; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013379:Substrate Specificity; D013816:Thermodynamics; D014364:Tryptophan / Q000031:analogs & derivatives* / Q000378:metabolism; D029968:Escherichia coli Proteins
chemical_list: D001426:Bacterial Proteins; D012097:Repressor Proteins; D014364:Tryptophan; C027190:TRPR protein, E coli; D029968:Escherichia coli Proteins; C027986:5-methoxytryptophan