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Evaluation of the substrate envelope hypothesis for inhibitors of HIV-1 protease

2007Journal article Open access
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dc.contributor.authorChellappan, Sripriya
dc.contributor.authorKairys, Visvaldas
dc.contributor.authorFernandes, Miguel X.
dc.contributor.authorSchiffer, Celia
dc.contributor.authorGilson, Michael K.
dc.date.accessioned2023-02-07T09:51:56Z
dc.date.available2023-02-07T09:51:56Z
dc.date.issued2007
dc.description.abstractCrystallographic data show that various substrates of HIV protease occupy a remarkably uniform region within the binding site; this region has been termed the substrate envelope. It has been suggested that an inhibitor that fits within the substrate envelope should tend to evade viral resistance because a protease mutation that reduces the affinity of the inhibitor will also tend to reduce the affinity of substrate, and will hence decrease the activity of the enzyme. Accordingly, inhibitors that fit the substrate envelope better should be less susceptible to clinically observed resistant mutations, since these must also allow substrates to bind. The present study describes a quantitative measure of the volume of a bound inhibitor falling outside the substrate envelope, and observes that this quantity correlates with the inhibitor’s losses in affinity to clinically relevant mutants. This measure may thus be use ful as a penalty function in the design of robust HIV protease inhibitors.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationChellappan, S., Kairys, V., Fernandes, M. X., Schiffer, C., & Gilson, M. K. (2007). Evaluation of the substrate envelope hypothesis for inhibitors of HIV‐1 protease. Proteins: structure, function, and bioinformatics, 68(2), 561-567.pt_PT
dc.identifier.doi10.1002/prot.21431pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.13/5005
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherWileypt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/pt_PT
dc.subjectResistancept_PT
dc.subjectAIDSpt_PT
dc.subjectDrug designpt_PT
dc.subjectMutantpt_PT
dc.subjectDockingpt_PT
dc.subject.pt_PT
dc.subjectFaculdade de Ciências Exatas e da Engenhariapt_PT
dc.titleEvaluation of the substrate envelope hypothesis for inhibitors of HIV-1 proteasept_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage567pt_PT
oaire.citation.issue2pt_PT
oaire.citation.startPage561pt_PT
oaire.citation.titleProteins: Structure, Function, and Bioinformaticspt_PT
oaire.citation.volume68pt_PT
person.familyNameKairys
person.familyNameFernandes
person.givenNameVisvaldas
person.givenNameMiguel Xavier
person.identifierK-9893-2013
person.identifier.ciencia-idA716-F916-AFB2
person.identifier.ciencia-idED1D-3C7A-467C
person.identifier.orcid0000-0002-5427-0175
person.identifier.orcid0000-0002-1840-616X
person.identifier.ridA-4373-2013
person.identifier.scopus-author-id6602925161
person.identifier.scopus-author-id35466972500
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication43821a45-10cf-4dbd-bc5a-fa88d146fc36
relation.isAuthorOfPublication8dab9a0d-f44a-4d2d-b9b1-7b3145162ca3
relation.isAuthorOfPublication.latestForDiscovery8dab9a0d-f44a-4d2d-b9b1-7b3145162ca3

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