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Computational improvement of small-molecule inhibitors of Bacillus anthracis protective antigen activation through isostere-based substitutions

2020-07Journal article Open access
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dc.contributor.authorSilva, Pedro J.
dc.contributor.authorSilva, Sandra V.R.L.
dc.date.accessioned2020-07-24T16:20:51Z
dc.date.available2020-07-24T16:20:51Z
dc.date.issued2020-07
dc.description.abstractThere has recently been interest in the development of small-molecule inhibitors of the oligomerization of Bacillus anthracis protective antigen for therapeutic use. Some of the proposed lead compounds have, however, unfavorable solubility in aqueous medium, which prevents their clinical use. In this computational work, we have designed several hundreds of derivatives with progressively higher hydro-solubility and tested their ability to dock the relevant binding cavity. The highest-ranking docking hits were then subjected to 125 nslong simulations to ascertain the stability of the binding modes. Several of the potential candidates performed quite disappointingly, but two molecules showed very stable binding modes throughout the complete simulations. Besides the identification of these two promising leads, these molecular dynamics simulations allowed the discovery of several insights that shall prove useful in the further improvement of these candidate towards higher potency and stability.pt_PT
dc.description.versioninfo:eu-repo/semantics/acceptedVersionpt_PT
dc.identifier.citationSilva, Sandra V.R.L. & Silva, Pedro J. (2020). Computational improvement of small-molecule inhibitors of Bacillus anthracis protective antigen activation through isostere-based substitutions, Journal of Biomolecular Structure and Dynamics, DOI: 10.1080/07391102.2020.1792987
dc.identifier.doi10.1080/07391102.2020.1792987pt_PT
dc.identifier.urihttp://hdl.handle.net/10284/8816
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherTaylor and Francispt_PT
dc.relation.publisherversionhttp://dx.doi.org/10.1080/07391102.2020.1792987pt_PT
dc.subjectAnthraxpt_PT
dc.subjectLead compoundspt_PT
dc.subjectMolecular dynamicspt_PT
dc.subjectDockingpt_PT
dc.titleComputational improvement of small-molecule inhibitors of Bacillus anthracis protective antigen activation through isostere-based substitutionspt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.titleJournal of Biomolecular Structure and Dynamicspt_PT
person.familyNameSilva
person.givenNamePedro
person.identifier.orcid0000-0001-9316-9275
person.identifier.scopus-author-id55310885700
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublicationf4a9230e-0a0e-45b6-b894-e71ded186ef2
relation.isAuthorOfPublication.latestForDiscoveryf4a9230e-0a0e-45b6-b894-e71ded186ef2

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