{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T21:57:17Z","timestamp":1781819837603,"version":"3.54.5"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"16","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,8,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Motivation: Mutating residues into alanine (alanine scanning) is one of the fastest experimental means of probing hypotheses about protein function. Alanine scans can reveal functional hot spots, i.e. residues that alter function upon mutation. In vitro mutagenesis is cumbersome and costly: probing all residues in a protein is typically as impossible as substituting by all non-native amino acids. In contrast, such exhaustive mutagenesis is feasible in silico.<\/jats:p>\n               <jats:p>Results: Previously, we developed SNAP to predict functional changes due to non-synonymous single nucleotide polymorphisms. Here, we applied SNAP to all experimental mutations in the ASEdb database of alanine scans; we identified 70% of the hot spots (\u22651 kCal\/mol change in binding energy); more severe changes were predicted more accurately. Encouraged, we carried out a complete all-against-all in silico mutagenesis for human glucokinase. Many of the residues predicted as functionally important have indeed been confirmed in the literature, others await experimental verification, and our method is ready to aid in the design of in vitro mutagenesis.<\/jats:p>\n               <jats:p>Availability: ASEdb and glucokinase scores are available at http:\/\/www.rostlab.org\/services\/SNAP. For submissions of large\/whole proteins for processing please contact the author.<\/jats:p>\n               <jats:p>Contact: \u00a0yb2009@columbia.edu<\/jats:p>","DOI":"10.1093\/bioinformatics\/btn268","type":"journal-article","created":{"date-parts":[[2008,8,9]],"date-time":"2008-08-09T13:08:02Z","timestamp":1218287282000},"page":"i207-i212","source":"Crossref","is-referenced-by-count":58,"title":["Comprehensive <i>in silico<\/i> mutagenesis highlights functionally important residues in proteins"],"prefix":"10.1093","volume":"24","author":[{"given":"Yana","family":"Bromberg","sequence":"first","affiliation":[{"name":"1 Department of Biochemistry Molecular Biophysics, Columbia University, 630 West 168th St, 2Columbia University Center for Computational Biology and Bioinformatics (C2B2) & Herbert Irving Cancer Center and 3NorthEast Structural Genomics Consortium (NESG) and New York Consortium on Membrane Protein Structure (NYCOMPS), Columbia University, 1130 St. Nicholas Ave. Rm. 802, New York, NY 10032, USA"},{"name":"1 Department of Biochemistry Molecular Biophysics, Columbia University, 630 West 168th St, 2Columbia University Center for Computational Biology and Bioinformatics (C2B2) & Herbert Irving Cancer Center and 3NorthEast Structural Genomics Consortium (NESG) and New York Consortium on Membrane Protein Structure (NYCOMPS), Columbia University, 1130 St. Nicholas Ave. Rm. 802, New York, NY 10032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Burkhard","family":"Rost","sequence":"additional","affiliation":[{"name":"1 Department of Biochemistry Molecular Biophysics, Columbia University, 630 West 168th St, 2Columbia University Center for Computational Biology and Bioinformatics (C2B2) & Herbert Irving Cancer Center and 3NorthEast Structural Genomics Consortium (NESG) and New York Consortium on Membrane Protein Structure (NYCOMPS), Columbia University, 1130 St. Nicholas Ave. Rm. 802, New York, NY 10032, USA"},{"name":"1 Department of Biochemistry Molecular Biophysics, Columbia University, 630 West 168th St, 2Columbia University Center for Computational Biology and Bioinformatics (C2B2) & Herbert Irving Cancer Center and 3NorthEast Structural Genomics Consortium (NESG) and New York Consortium on Membrane Protein Structure (NYCOMPS), Columbia University, 1130 St. Nicholas Ave. Rm. 802, New York, NY 10032, USA"},{"name":"1 Department of Biochemistry Molecular Biophysics, Columbia University, 630 West 168th St, 2Columbia University Center for Computational Biology and Bioinformatics (C2B2) & Herbert Irving Cancer Center and 3NorthEast Structural Genomics Consortium (NESG) and New York Consortium on Membrane Protein Structure (NYCOMPS), Columbia University, 1130 St. Nicholas Ave. Rm. 802, New York, NY 10032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2008,8,9]]},"reference":[{"key":"2023020210500088900_B1","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1093\/nar\/28.1.45","article-title":"The SWISS-PROT protein sequence database and its supplement TrEMBL in 2000","volume":"28","author":"Bairoch","year":"2000","journal-title":"Nucleic Acids Res"},{"key":"2023020210500088900_B2","doi-asserted-by":"crossref","first-page":"D154","DOI":"10.1093\/nar\/gki070","article-title":"The universal protein resource (UniProt)","volume":"33","author":"Bairoch","year":"2005","journal-title":"Nucleic Acids Res"},{"key":"2023020210500088900_B3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1006\/jmbi.1998.1843","article-title":"Anatomy of hot spots in protein interfaces","volume":"280","author":"Bogan","year":"1998","journal-title":"J. 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