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UNIVERSITY OF BUCHAREST
FACULTY OF PHYSICS Guest
2024-11-23 17:44 |
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Conference: Bucharest University Faculty of Physics 2023 Meeting
Section: Biophysics; Medical Physics
Title:
Calcitonin receptors in hydrated lipid membranes
Authors:
Denisa-Sonia ANDRONIC(1), Ana-Nicoleta BONDAR(1, 2)
Affiliation:
1) University of Bucharest, Faculty of Physics,
2)Forschungszentrum Jülich, Computational Biomedicine (IAS-5/INM-9)
E-mail
denisa.andronic@s.unibuc.ro
Keywords:
G protein-coupled receptors, calcitonin, computational biomedicine, MD simulations
Abstract:
G Protein-Coupled Receptors (GPCRs) are the largest family of membrane receptors with a great functional diversity. They mediate the biological effects of hormones, neurotransmitters, odorants, as well as of visual stimuli. Therefore, GPCRs turn into essential drug targets and every year approximately one third of the approved and marketed drugs are in fact modulating the activity of a GPCR [1]. Involving the great power of computers helps us get insight into the high specificity of GPCRs, study their conformational dynamics and make predictions about their signaling pathways. One peptide hormone that binds to a class B GPCR is calcitonin. It has a key role in regulating the calcium concentration in blood and it is used as a therapeutic drug for hypercalcemia, osteoporosis and Paget’s disease [2, 3]. This work presents the main steps of preparing a protein – membrane system that is suitable for undergoing Molecular Dynamics (MD) simulations. It covers the study of the architecture of both calcitonin and the calcitonin receptor starting from an initial set of Cartesian coordinates, the prediction of the 3D structure of the whole receptor – G protein complex using Artificial Intelligence and the insertion of the receptor into a POPC bilayer that is hydrated on both sides.
References:
[1] Santos, R., Ursu, O., Gaulton, A. et al. A comprehensive map of molecular drug targets. Nat Rev Drug Discov 16, 19–34 (2017). https://doi.org/10.1038/nrd.2016.230
[2] Felsenfeld AJ, Levine BS. Calcitonin, the forgotten hormone: does it deserve to be forgotten? Clin Kidney J. 2015 Apr;8(2):180-7. doi: 10.1093/ckj/sfv011. Epub 2015 Mar 20. PMID: 25815174; PMCID: PMC4370311.
[3] Danila R, Livadariu R, Branisteanu D. CALCITONIN REVISITED IN 2020. Acta Endocrinol (Buchar). 2019 Oct-Dec;15(4):544-548. doi: 10.4183/aeb.2019.544. PMID: 32377257; PMCID: PMC7200115.
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