{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T20:33:59Z","timestamp":1772138039745,"version":"3.50.1"},"reference-count":25,"publisher":"Oxford University Press (OUP)","issue":"20","license":[{"start":{"date-parts":[[2020,7,19]],"date-time":"2020-07-19T00:00:00Z","timestamp":1595116800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"UK EPSRC","award":["EP\/N024796\/1"],"award-info":[{"award-number":["EP\/N024796\/1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,12,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Motivation<\/jats:title>\n                    <jats:p>Evolution couples differences in ambient pH to biological function through protonatable groups, in particular, those that switch from buried to exposed and alter protonation state in doing so. We present a tool focusing on structure-based discovery and display of these groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Since prediction of buried group pKas is computationally intensive, solvent accessibility of ionizable groups is displayed, from which the user can iteratively select pKa calculation centers. Results are color-coded, with emphasis on buried groups. Utility is demonstrated with benchmarking against known pH sensing sites in influenza virus hemagglutinin and in variants of murine hepatitis virus, a coronavirus. A pair of histidine residues, which are conserved in coronavirus spike proteins, are predicted to be electrostatically frustrated at acidic pH in both pre- and post-fusion conformations. We suggest that an intermediate expanded conformation at endosomal pH could relax the frustration, allowing histidine protonation and facilitating conformational conversion of coronavirus spike protein.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Availability and implementation<\/jats:title>\n                    <jats:p>This tool is available at http:\/\/www.protein-sol.manchester.ac.uk\/pka\/.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btaa646","type":"journal-article","created":{"date-parts":[[2020,7,13]],"date-time":"2020-07-13T07:28:52Z","timestamp":1594625332000},"page":"5112-5114","source":"Crossref","is-referenced-by-count":14,"title":["Protein-sol pKa: prediction of electrostatic frustration, with application to coronaviruses"],"prefix":"10.1093","volume":"36","author":[{"given":"Max","family":"Hebditch","sequence":"first","affiliation":[{"name":"School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Institute of Biotechnology , Manchester M1 7DN, UK"}]},{"given":"Jim","family":"Warwicker","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Institute of Biotechnology , Manchester M1 7DN, UK"}]}],"member":"286","published-online":{"date-parts":[[2020,7,19]]},"reference":[{"key":"2023062408141736800_btaa646-B1","doi-asserted-by":"crossref","first-page":"3260","DOI":"10.1002\/prot.23189","article-title":"Progress in the prediction of pKa values in proteins","volume":"79","author":"Alexov","year":"2011","journal-title":"Proteins"},{"key":"2023062408141736800_btaa646-B2","doi-asserted-by":"crossref","first-page":"10219","DOI":"10.1021\/bi00496a010","article-title":"pKa\u2019s of ionisable groups in proteins: atomic detail from a continuum electrostatic model","volume":"29","author":"Bashford","year":"1990","journal-title":"Biochemistry"},{"key":"2023062408141736800_btaa646-B3","doi-asserted-by":"crossref","first-page":"5804","DOI":"10.1073\/pnas.88.13.5804","article-title":"Protonation of interacting residues in a protein by a Monte Carlo method: application to lysozyme and the photosynthetic reaction center of Rhodobacter sphaeroides","volume":"88","author":"Beroza","year":"1991","journal-title":"Proc. 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