Predicting the reactivity of proteins from their sequence alone: Kazal family of protein inhibitors of serine proteinases

Proc Natl Acad Sci U S A. 2001 Feb 13;98(4):1410-5. doi: 10.1073/pnas.98.4.1410. Epub 2001 Feb 6.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Algorithms*
  • Amino Acid Sequence
  • Animals
  • Bacterial Proteins
  • Binding Sites
  • Cattle
  • Chymotrypsin / metabolism
  • Humans
  • Leukocyte Elastase / metabolism
  • Molecular Sequence Data
  • Ovomucin / metabolism*
  • Pancreatic Elastase / metabolism
  • Serine Endopeptidases / metabolism*
  • Subtilisins / metabolism
  • Trypsin Inhibitors / metabolism*

Substances

  • Bacterial Proteins
  • Trypsin Inhibitors
  • Ovomucin
  • Serine Endopeptidases
  • Subtilisins
  • Chymotrypsin
  • alpha-chymotrypsin
  • Pancreatic Elastase
  • Leukocyte Elastase
  • streptogrisin A