Computational predictions suggest that structural similarity in viral polymerases may lead to comparable allosteric binding sites.

Simple item page
dc.contributor.authorBrown, J. A.
dc.contributor.authorEspiritu, M. V.
dc.contributor.authorAbraham, J.
dc.contributor.authorThorpe, I. F.
dc.date.accessioned2018-09-21T19:12:39Z
dc.date.available2018-09-21T19:12:39Z
dc.date.issued2016-06-01
dc.description.abstractThe identification of ligand-binding sites is often the first step in drug targeting and design. To date there are numerous computational tools available to predict ligand binding sites. These tools can guide or mitigate the need for experimental methods to identify binding sites, which often require significant resources and time. Here, we evaluate four ligand-binding site predictor (LBSP) tools for their ability to predict allosteric sites within the Hepatitis C Virus (HCV) polymerase. Our results show that the LISE LBSP is able to identify all three target allosteric sites within the HCV polymerase as well as a known allosteric site in the Coxsackievirus polymerase. LISE was then employed to identify novel binding sites within the polymerases of the Dengue, West Nile, and Foot-and-mouth Disease viruses. Our results suggest that all three viral polymerases have putative sites that share structural or chemical similarities with allosteric pockets of the HCV polymerase. Thus, these binding locations may represent an evolutionarily conserved structural feature of several viral polymerases that could be exploited for the development of small molecule therapeutics.en_US
dc.description.sponsorshipJodian A. Brown was funded by NIH F31 pre-doctoral grant (GM-106958). We wish to thank Paul Zhong-ru Xie for his technical assistance regarding the LISE program.en_US
dc.description.urihttps://europepmc.org/abstract/med/27262620en_US
dc.format.extent33 pagesen_US
dc.genrejournal article pre-printen_US
dc.identifierdoi:10.13016/M2930NZ78
dc.identifier.citationJ. A. Brown, M. V. Espiritu, J. Abraham, and I. F. Thorpe. Computational Predictions suggest that Structural Similarity in Viral Polymerases may lead to Comparable Allosteric Binding Sites. Virus Research, 222; 80-93 (2016), doi: 10.1016/j.virusres.2016.05.029en_US
dc.identifier.uri10.1016/j.virusres.2016.05.029
dc.identifier.urihttp://hdl.handle.net/11603/11354
dc.language.isoen_USen_US
dc.publisherElsevieren_US
dc.relation.isAvailableAtThe University of Maryland, Baltimore County (UMBC)
dc.relation.ispartofUMBC Chemistry & Biochemistry Department Collection
dc.relation.ispartofUMBC Faculty Collection
dc.subjectdrug targetingen_US
dc.subjectligand-binding site predictor (LBSP)en_US
dc.subjectCoxsackievirus polymeraseen_US
dc.subjectUMBC High Performance Computing Facility (HPCF)en_US
dc.subjectproteins responsible for human disease
dc.subjectsites on proteins where small molecules may bind
dc.subjectHepatitis C virus (HCV) polymerase
dc.subjecttarget allosteric sites within the HCV polymerase
dc.subjectallosteric site in the Coxsackievirus polymerase
dc.subjectDengue
dc.subjectWest Nile
dc.subjectFoot-and mouth
dc.titleComputational predictions suggest that structural similarity in viral polymerases may lead to comparable allosteric binding sites.en_US
dc.typeTexten_US

Files

License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
1.68 KB
Format:
Item-specific license agreed upon to submission
Description:
Download

Collections

UMBC Chemistry & Biochemistry Department
UMBC Faculty Collection