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dc.contributor.authorEsşiz, Şebnem
dc.contributor.authorGencel, Melis
dc.contributor.authorAktolun, Muhammed
dc.contributor.authorDemir, Ayhan
dc.contributor.authorCarpenter, Timothy S.
dc.contributor.authorServili, Burak
dc.date.accessioned2021-05-24T16:46:22Z
dc.date.available2021-05-24T16:46:22Z
dc.date.issued2021
dc.identifier.issn1610-2940
dc.identifier.urihttps://hdl.handle.net/20.500.12469/4030
dc.description.abstractN-Methyl-D-aspartate receptors (NMDARs) are glutamate-gated ion channels found in the nerve cell membranes. As a result of overexcitation of NMDARs, neuronal death occurs and may lead to diseases such as epilepsy, stroke, Alzheimer's disease, and Parkinson's disease. In this study, human GluN1- GluN2A type NMDAR structure is modeled based on the X-ray structure of the Xenopus laevis template and missing loops are added by ab-initio loop modeling. The final structure is chosen according to two different model assessment scores. To be able to observe the structural changes upon ligand binding, glycine and glutamate molecules are docked into the corresponding binding sites of the receptor. Subsequently, molecular dynamics simulations of 1.3 mu s are performed for both apo and ligand-bound structures. Structural parameters, which have been considered to show functionally important changes in previous NMDAR studies, are monitored as conformational rulers to understand the dynamics of the conformational changes. Moreover, principal component analysis (PCA) is performed for the equilibrated part of the simulations. From these analyses, the differences in between apo and ligand-bound simulations can be summarized as the following: The girdle right at the beginning of the pore loop, which connects M2 and M3 helices of the ion channel, partially opens. Ligands act like an adhesive for the ligand-binding domain (LBD) by keeping the bi-lobed structure together and consequently this is reflected to the overall dynamics of the protein as an increased correlation of the LBD with especially the amino-terminal domain (ATD) of the protein.en_US
dc.language.isoEnglishen_US
dc.publisherSPRINGERen_US
dc.subjectLigand gated ion channelsen_US
dc.subjectIonotropic glutamate receptorsen_US
dc.subjectMolecular dynamicsen_US
dc.subjectPrincipal component analysisen_US
dc.subjectHomology and loop modelingen_US
dc.titleCorrelated conformational dynamics of the human GluN1-GluN2A type N-methyl-D-aspartate (NMDA) receptoren_US
dc.typeArticleen_US
dc.relation.journalJOURNAL OF MOLECULAR MODELINGen_US
dc.identifier.issue6en_US
dc.identifier.volume27en_US
dc.identifier.wos000648486700001en_US
dc.identifier.doi10.1007/s00894-021-04755-8en_US
dc.contributor.khasauthorEşsiz, Şebnemen_US
dc.contributor.khasauthorGencel, Melisen_US
dc.contributor.khasauthorAktolun, Muhammeden_US
dc.contributor.khasauthorDemir, Ayhanen_US
dc.contributor.khasauthorServili, Buraken_US


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