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dc.contributor.authorNeuwald, A.F.
dc.contributor.authorAravind, L.
dc.contributor.authorAltschul, S.F.
dc.date.accessioned2019-04-29T19:00:57Z
dc.date.available2019-04-29T19:00:57Z
dc.date.issued2018
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85042097928&doi=10.7554%2feLife.29880&partnerID=40&md5=3a3e0b7d7557c544bff4e29091980888
dc.identifier.urihttp://hdl.handle.net/10713/8896
dc.description.abstractResidues responsible for allostery, cooperativity, and other subtle but functionally important interactions remain difficult to detect. To aid such detection, we employ statistical inference based on the assumption that residues distinguishing a protein subgroup from evolutionarily divergent subgroups often constitute an interacting functional network. We identify such networks with the aid of two measures of statistical significance. One measure aids identification of divergent subgroups based on distinguishing residue patterns. For each subgroup, a second measure identifies structural interactions involving pattern residues. Such interactions are derived either from atomic coordinates or from Direct Coupling Analysis scores, used as surrogates for structural distances. Applying this approach to N-acetyltransferases, P-loop GTPases, RNA helicases, synaptojanin-superfamily phosphatases and nucleases, and thymine/uracil DNA glycosylases yielded results congruent with biochemical understanding of these proteins, and also revealed striking sequence-structural features overlooked by other methods. These and similar analyses can aid the design of drugs targeting allosteric sites. Copyright 2018, eLife Sciences Publications Ltd. All rights reserved.en_US
dc.description.sponsorshipLA and SFA were supported by the Intramural Research Program of the National Institutes of Health, National Library of Medicine. AFN received no specific funding for this work, but was supported by the University of Maryland, Baltimore. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.en_US
dc.description.urihttps://dx.doi.org/10.7554/eLife.29880en_US
dc.language.isoen_USen_US
dc.publishereLife Sciences Publications Ltden_US
dc.relation.ispartofeLife
dc.subjectComputational Biologyen_US
dc.subjectEnzymesen_US
dc.subjectProtein Conformationen_US
dc.titleInferring joint sequence-structural determinants of protein functional specificityen_US
dc.typeArticleen_US
dc.identifier.doi10.7554/eLife.29880
dc.identifier.pmid29336305


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