title: Predicting the reactivity of proteins from their sequence alone: Kazal family of protein inhibitors of serine proteinases.
abstract: An additivity-based sequence to reactivity algorithm for the interaction of members of the Kazal family of protein inhibitors with six selected serine proteinases is described. Ten consensus variable contact positions in the inhibitor were identified, and the 19 possible variants at each of these positions were expressed. The free energies of interaction of these variants and the wild type were measured. For an additive system, this data set allows for the calculation of all possible sequences, subject to some restrictions. The algorithm was extensively tested. It is exceptionally fast so that all possible sequences can be predicted. The strongest, the most specific possible, and the least specific inhibitors were designed, and an evolutionary problem was solved.
authors.affiliation: Department of Chemistry, Purdue University, 1393 Brown Building, West Lafayette, IN 47907-1393, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Lu
authors.forename: W
authors.initials: W
authors.lastname: Lu
authors.forename: M A
authors.initials: MA
authors.lastname: Qasim
authors.forename: S
authors.initials: S
authors.lastname: Anderson
authors.forename: I
authors.initials: I
authors.lastname: Apostol
authors.forename: W
authors.initials: W
authors.lastname: Ardelt
authors.forename: T
authors.initials: T
authors.lastname: Bigler
authors.forename: Y W
authors.initials: YW
authors.lastname: Chiang
authors.forename: J
authors.initials: J
authors.lastname: Cook
authors.forename: M N
authors.initials: MN
authors.lastname: James
authors.forename: I
authors.initials: I
authors.lastname: Kato
authors.forename: C
authors.initials: C
authors.lastname: Kelly
authors.forename: W
authors.initials: W
authors.lastname: Kohr
authors.forename: T
authors.initials: T
authors.lastname: Komiyama
authors.forename: T Y
authors.initials: TY
authors.lastname: Lin
authors.forename: M
authors.initials: M
authors.lastname: Ogawa
authors.forename: J
authors.initials: J
authors.lastname: Otlewski
authors.forename: S J
authors.initials: SJ
authors.lastname: Park
authors.forename: S
authors.initials: S
authors.lastname: Qasim
authors.forename: M
authors.initials: M
authors.lastname: Ranjbar
authors.forename: M
authors.initials: M
authors.lastname: Tashiro
authors.forename: N
authors.initials: N
authors.lastname: Warne
authors.forename: H
authors.initials: H
authors.lastname: Whatley
authors.forename: A
authors.initials: A
authors.lastname: Wieczorek
authors.forename: M
authors.initials: M
authors.lastname: Wieczorek
authors.forename: T
authors.initials: T
authors.lastname: Wilusz
authors.forename: R
authors.initials: R
authors.lastname: Wynn
authors.forename: W
authors.initials: W
authors.lastname: Zhang
authors.forename: M
authors.initials: M
authors.lastname: Laskowski
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins; D001665:Binding Sites; D002417:Cattle; D002918:Chymotrypsin / Q000378:metabolism; D006801:Humans; D019272:Leukocyte Elastase / Q000378:metabolism; D008969:Molecular Sequence Data; D010059:Ovomucin / Q000378:metabolism*; D010196:Pancreatic Elastase / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism*; D013381:Subtilisins / Q000378:metabolism; D014361:Trypsin Inhibitors / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D014361:Trypsin Inhibitors; D010059:Ovomucin; D012697:Serine Endopeptidases; D013381:Subtilisins; D002918:Chymotrypsin; C117608:alpha-chymotrypsin; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase; C024983:streptogrisin A