{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T19:49:34Z","timestamp":1776023374589,"version":"3.50.1"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"22","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2007,11,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Motivation: There is a need for an efficient and accurate computational method to identify the effects of single- and multiple-residue mutations on the stability and reactivity of proteins. Such a method should ideally be consistent and yet applicable in a widespread manner, i.e. it should be applied to various proteins under the same parameter settings, and have good predictive power for all of them.<\/jats:p><jats:p>Results: We develop a Delaunay tessellation-based four-body scoring function to predict the effects of single- and multiple-residue mutations on the stability and reactivity of proteins. We test our scoring function on sets of single-point mutations used by several previous studies. We also assemble a new, diverse set of 237 single- and multiple-residue mutations, from over 24 different publications. The four-body scoring function correctly predicted the changes to the stability of 169 out of 210 mutants (80.5%), and the changes to the reactivity of 17 out of 27 mutants (63%). For the mutants that had the changes in stability\/reactivity quantified (using reaction rates, temperatures, etc.), an average Spearman rank correlation coefficient of 0.67 was achieved with the four-body scores. We also develop an efficient method for screening huge numbers of mutants of a protein, called combinatorial mutagenesis. In one study, 64 million mutants of a cold-shock nucleus binding domain protein 1CSQ, with six of its residues being changed to all possible (20) amino acids, were screened within a few hours on a PC, and all five stabilizing mutants reported were correctly identified as stabilizing by combinatorial mutagenesis.<\/jats:p><jats:p>Availability: All lists of mutants scored, and executables of programs developed as part of this study are available from this web page: http:\/\/www.wsu.edu\/~kbala\/Mutate.html<\/jats:p><jats:p>Contact: \u00a0kbala@wsu.edu or bkrishna@math.wsu.edu<\/jats:p><jats:p>Supplementary information: Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btm481","type":"journal-article","created":{"date-parts":[[2007,10,7]],"date-time":"2007-10-07T00:24:16Z","timestamp":1191716656000},"page":"3009-3015","source":"Crossref","is-referenced-by-count":41,"title":["Four-Body Scoring Function for Mutagenesis"],"prefix":"10.1093","volume":"23","author":[{"given":"Chris","family":"Deutsch","sequence":"first","affiliation":[{"name":"Department of Mathematics, Washington State University, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bala","family":"Krishnamoorthy","sequence":"additional","affiliation":[{"name":"Department of Mathematics, Washington State University, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2007,10,5]]},"reference":[{"key":"2023041208253995800_","doi-asserted-by":"crossref","first-page":"27553","DOI":"10.1074\/jbc.M111777200","article-title":"Structural basis of thermostability analysis of stabilizing mutations in subtilisin bpn","volume":"277","author":"Almog","year":"2002","journal-title":"J. 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