Durdagi Serdar, Erol Ismail, Salmas Ramin Ekhteiari, Aksoydan Busecan, Kantarcioglu Isik
Computational Biology and Molecular Simulations Laboratory, Department of Biophysics, School of Medicine, Bahcesehir University (BAU), Istanbul, Turkey; Neuroscience Program, Graduate School of Health Sciences, Bahcesehir University, Istanbul, Turkey.
Computational Biology and Molecular Simulations Laboratory, Department of Biophysics, School of Medicine, Bahcesehir University (BAU), Istanbul, Turkey; Department of Chemistry, Gebze Technical University, Kocaeli, Turkey.
Neurosci Lett. 2019 May 1;700:30-37. doi: 10.1016/j.neulet.2018.04.028. Epub 2018 Apr 20.
G Protein-Coupled Receptors (GPCRs) can form homo- and heterodimers or constitute higher oligomeric clusters with other heptahelical GPCRs. In this article, multiscale molecular modeling approaches as well as experimental techniques which are used to study oligomerization of GPCRs are reviewed. In particular, the effect of dimerization/oligomerization to the ligand binding affinity of individual protomers and also on the efficacy of the oligomer are discussed by including diverse examples from the literature. In addition, possible allosteric effects that may emerge upon interaction of GPCRs with membrane components, like cholesterol, is also discussed. Investigation of these above-mentioned interactions may greatly contribute to the candidate molecule screening studies and development of novel therapeutics with fewer adverse effects.
G蛋白偶联受体(GPCRs)可形成同二聚体和异二聚体,或与其他七螺旋GPCRs构成更高阶的寡聚簇。本文综述了用于研究GPCRs寡聚化的多尺度分子建模方法以及实验技术。特别地,通过纳入文献中的各种实例,讨论了二聚化/寡聚化对单个原聚体配体结合亲和力以及寡聚体功效的影响。此外,还讨论了GPCRs与膜成分(如胆固醇)相互作用时可能出现的变构效应。对上述相互作用的研究可能会极大地促进候选分子筛选研究以及开发副作用更少的新型疗法。