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dc.contributor.authorHaddad, Yazan Abdulmajeed Eyadhcs
dc.contributor.authorHeger, Zbyněkcs
dc.contributor.authorAdam, Vojtěchcs
dc.date.accessioned2020-08-04T11:04:07Z
dc.date.available2020-08-04T11:04:07Z
dc.date.issued2017-01-20cs
dc.identifier.citationFrontiers in Molecular Neuroscience. 2017, vol. 10, issue 7, p. 1-7.en
dc.identifier.issn1662-5099cs
dc.identifier.other134300cs
dc.identifier.urihttp://hdl.handle.net/11012/69379
dc.description.abstractTargeted therapy is a promising approach for treatment of neuroblastoma as evident from the large number of targeting agents employed in clinical practice today. In the absence of known crystal structures, researchers rely on homology modeling to construct template-based theoretical structures for drug design and testing. Here, we discuss three candidate cell surface proteins that are suitable for homology modeling: human norepinephrine transporter (hNET), anaplastic lymphoma kinase (ALK), and neurotrophic tyrosine kinase receptor 2 (NTRK2 or TrkB). When choosing templates, both sequence identity and structure quality are important for homology modeling and pose the first of many challenges in the modeling process. Homology modeling of hNET can be improved using template models of dopamine and serotonin transporters instead of the leucine transporter (LeuT). The extracellular domains of ALK and TrkB are yet to be exploited by homology modeling. There are several idiosyncrasies that require direct attention throughout the process of model construction, evaluation and refinement. Shifts/gaps in the alignment between the template and target, backbone outliers and side-chain rotamer outliers are among the main sources of physical errors in the structures. Low-conserved regions can be refined with loop modeling method. Residue hydrophobicity, accessibility to bound metals or glycosylation can aid in model refinement. We recommend resolving these idiosyncrasies as part of “good modeling practice” to obtain highest quality model. Decreasing physical errors in protein structures plays major role in the development of targeting agents and understanding of chemical interactions at the molecular level.en
dc.formattextcs
dc.format.extent1-7cs
dc.format.mimetypeapplication/pdfcs
dc.language.isoencs
dc.publisherFrontierscs
dc.relation.ispartofFrontiers in Molecular Neurosciencecs
dc.relation.urihttp://journal.frontiersin.org/article/10.3389/fnmol.2017.00007/fullcs
dc.rightsCreative Commons Attribution 4.0 Internationalcs
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/cs
dc.subjectneuroblastomaen
dc.subjecttargeted therapyen
dc.subjecthomology modelingen
dc.subjectnorepinephrine transporteren
dc.subjectanaplastic lymphoma kinaseen
dc.subjectneurotrophic tyrosine kinase receptoren
dc.titleTargeting Neuroblastoma Cell Surface Proteins: Recommendations for Homology Modeling of hNET, ALK, and TrkBen
thesis.grantorVysoké učení technické v Brně. Středoevropský technologický institut VUT. Chytré nanonástrojecs
sync.item.dbidVAV-134300en
sync.item.dbtypeVAVen
sync.item.insts2021.11.22 12:54:48en
sync.item.modts2021.11.22 12:25:52en
dc.coverage.issue7cs
dc.coverage.volume10cs
dc.identifier.doi10.3389/fnmol.2017.00007cs
dc.rights.accessopenAccesscs
dc.rights.sherpahttp://www.sherpa.ac.uk/romeo/issn/1662-5099/cs
dc.type.driverarticleen
dc.type.statusPeer-revieweden
dc.type.versionpublishedVersionen


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Creative Commons Attribution 4.0 International
Except where otherwise noted, this item's license is described as Creative Commons Attribution 4.0 International