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

Stephen M. Lu, Wuyuan Lu, M. A. Qasim, Stephen Anderson, Izydor Apostol, Wojciech Ardelt, Theresa Bigler, Yi Wen Chiang, James Cook, Michael N.G. James, Ikunoshin Kato, Clyde Kelly, William Kohr, Tomoko Komiyama, Tiao-Yin Lin, Michio Ogawa, Jacek Otlewski, Soon Jae Park, Sabiha Qasim, Michael RanjbarMisao Tashiro, Nicholas Warne, Harry Whatley, Anna Wieczorek, Maciej Wieczorek, Tadeusz Wilusz, Richard Wynn, Wenlei Zhang, Michael Laskowski*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

91 Scopus citations

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.

Original languageEnglish
Pages (from-to)1410-1415
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume98
Issue number4
DOIs
StatePublished - 13 Feb 2001

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