dc.creator | Senćanski, Milan | |
dc.creator | Vrecl, Milka | |
dc.creator | Veljković, Nevena V. | |
dc.creator | Glišić, Sanja | |
dc.date.accessioned | 2023-05-26T06:49:10Z | |
dc.date.accessioned | 2023-05-26T07:02:14Z | |
dc.date.available | 2023-05-26T06:49:10Z | |
dc.date.available | 2023-05-26T07:02:14Z | |
dc.date.issued | 2018 | |
dc.identifier.issn | 2334-6590 | |
dc.identifier.uri | https://vinar.vin.bg.ac.rs/handle/123456789/11013 | |
dc.description.abstract | Stabilization of specific G-protein coupled receptor (GPCR) conformation is achieved by ligand binding to orthosteric or allosteric sites on a GPCRs. A crucial unresolved issue in GPCRs activation/signaling is the role of receptor structural conformations in G protein/effector protein selection. One of the possible approaches to get comprehensive depiction of GPCRs activation dynamics are molecular simulations and recently described nanobody-derived intrabodies. Monomeric single-domain antibody (nanobody) from the Camelid family was found to allosterically bind to and stabilizes distinct conformational states of the β2AR. By applying informational spectrum method (ISM), a virtual spectroscopy method for investigation of the protein-protein interactions, we have designed peptide mimetic of the nanobody related to the β2AR (nanobody derived peptide, NDP). Further, interaction between NDP and the ligand-bound β2AR active conformation have been studied by protein-peptide docking, molecular dynamics simulations and metadynamics calculations of free energy binding. Finally, the affinity of selected NDPs towards agonist-activated β2AR was also studied by microscale thermophoresis (MST) and by bioluminescence resonance energy transfer (BRET) based β-arrestin 2 recruitment assay. MST data predicted micromolar range interaction of selected NDPs with the β2AR, while the preliminary β-arrestin 2 recruitment results suggest prospective further modification and optimization of NDPs toward effective modulators of the β2AR. | en |
dc.language.iso | en | |
dc.publisher | Department of Biology and Ecology : Faculty of Sciences University of Novi Sad | |
dc.relation | info:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/173001/RS// | |
dc.rights | openAccess | |
dc.source | Biologia Serbica : Belgrade BioInformatics Conference : BelBi2018 : program and the book of abstracts; June 18-22 | |
dc.subject | bioinformatics | en |
dc.subject | informational spectrum method | en |
dc.subject | molecular dynamics simulations | en |
dc.subject | nanobody derived peptides | en |
dc.subject | protein-protein interactions | en |
dc.title | Combined in silico and experimental approach to identify the peptide mimetic of the nanobody that stabilize functional conformational state of the beta2 adrenergic receptor (β2AR) | en |
dc.type | conferenceObject | |
dc.rights.license | ARR | |
dc.citation.volume | 40 | |
dc.citation.issue | 1 | |
dc.citation.spage | 58 | |
dc.description.other | Special Edition of Book of Abstracts | |
dc.type.version | publishedVersion | |
dc.identifier.fulltext | http://vinar.vin.bg.ac.rs/bitstream/id/29532/sencanski_2.pdf | |
dc.identifier.rcub | https://hdl.handle.net/21.15107/rcub_vinar_11013 | |