{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T22:19:53Z","timestamp":1762899593353},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"17","license":[{"start":{"date-parts":[[2018,9,1]],"date-time":"2018-09-01T00:00:00Z","timestamp":1535760000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/about_us\/legal\/notices"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Motivation<\/jats:title>\n                  <jats:p>Single amino acid variations (SAVs) in protein\u2013protein interaction (PPI) sites play critical roles in diseases. PPI sites (interfaces) have a small subset of residues called hot spots that contribute significantly to the binding energy, and they may form clusters called hot regions. Singlet hot spots are the single amino acid hot spots outside of the hot regions. The distribution of SAVs on the interface residues may be related to their disease association.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We performed statistical and structural analyses of SAVs with literature curated experimental thermodynamics data, and demonstrated that SAVs which destabilize PPIs are more likely to be found in singlet hot spots rather than hot regions and energetically less important interface residues. In contrast, non-hot spot residues are significantly enriched in neutral SAVs, which do not affect PPI stability. Surprisingly, we observed that singlet hot spots tend to be enriched in disease-causing SAVs, while benign SAVs significantly occur in non-hot spot residues. Our work demonstrates that SAVs in singlet hot spot residues have significant effect on protein stability and function.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Availability and implementation<\/jats:title>\n                  <jats:p>The dataset used in this paper is available as Supplementary Material. The data can be found at http:\/\/prism.ccbb.ku.edu.tr\/data\/sav\/ as well.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Supplementary information<\/jats:title>\n                  <jats:p>Supplementary data are available at Bioinformatics online.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/bioinformatics\/bty569","type":"journal-article","created":{"date-parts":[[2018,7,7]],"date-time":"2018-07-07T06:00:37Z","timestamp":1530943237000},"page":"i795-i801","source":"Crossref","is-referenced-by-count":22,"title":["Analysis of single amino acid variations in singlet hot spots of protein\u2013protein interfaces"],"prefix":"10.1093","volume":"34","author":[{"given":"E Sila","family":"Ozdemir","sequence":"first","affiliation":[{"name":"Department of Chemical and Biological Engineering, Koc University, Istanbul, Turkey"}]},{"given":"Attila","family":"Gursoy","sequence":"additional","affiliation":[{"name":"Department of Computer Engineering, Koc University, Istanbul, Turkey"},{"name":"Research Center for Translational Medicine (KUTTAM), Koc University, Istanbul, Turkey"}]},{"given":"Ozlem","family":"Keskin","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biological Engineering, Koc University, Istanbul, Turkey"},{"name":"Research Center for Translational Medicine (KUTTAM), Koc University, Istanbul, Turkey"}]}],"member":"286","published-online":{"date-parts":[[2018,9,8]]},"reference":[{"key":"2023061313494264100_bty569-B1","first-page":"Unit7 20","article-title":"Predicting functional effect of human missense mutations using PolyPhen-2","author":"Adzhubei","year":"2013","journal-title":"Curr. 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