title

مدل سازی مولکولی گیرنده CCR2در غشاء دو لایه ای پالمیتوئیل اولئیل گلیسرو فسفوکولین

عبادی, احمد and دستان, دارا and اعظمی, مجتبی and کریمی, ادیبه and رزاقی اصل, نیما (1396) مدل سازی مولکولی گیرنده CCR2در غشاء دو لایه ای پالمیتوئیل اولئیل گلیسرو فسفوکولین. Structural Chemistry ــ 28 (3). pp. 849-857. شاپا 1040-0400

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Official URL: http://link.springer.com/journal/11224


Title

Molecular modeling of human CCR2 receptor within POPC lipid bilayer.

English Abstract

Chemokine receptor 2 (CCR2), a G-protein coupled receptor (GPCR), is a critical target for several inflammatory and autoimmune diseases. The main restriction on designing desirable antagonists against CCR2 is the lack of appropriate crystal structure for this target. In the absence of such experimental data, computational methods triggering structure prediction provide a cost-effective option. Homology modeling has been widely used to explore GPCR structure. Within the present contribution, homology modeling, molecular docking and molecular dynamics (MD) simulation were applied to construct a reliable model for CCR2. In the present contribution, we docked INCB3344, one of the most potent CCR2 inhibitors, into the active site of the CCR2 protein. Subsequently, we studied the dynamic behavior of INCB3344-CCR2 complex in the presence of lipid membrane. Moreover; a detailed molecular mechanism of INCB3344 action has been proposed. It was revealed that Tyr120, His121, Tyr259 and Glu291 formed H-bond interactions with INCB3344 while residues such as Trp98, His202, Thr203 and Thr173 participated in hydrophobic interactions. As a consequence, a reliable homology model of CCR2 could be successfully developed on the basis of CCR5 crystallographic structure. Finally it was found that binding of INCB3344 led to the structural changes in CCR2 that provided more interaction sites. Results of this study may be useful to design further CCR2 inhibiting structures with the aim of developing desirable therapeutic agents.

Item Type:Article
زبان سند : انگلیسی
نویسنده اول :احمد عبادی
نویسنده مسئول :نیما رزاقی اصل
Additional Information:Impact Factor (2016) 1.582 Indexed in: ISI, Scopus, Chemical Abstracts Service (CAS), Google Scholar, EBSCO Discovery Service, Academic OneFile, Academic Search, Chimica,CSA Environmental Sciences, Current Contents/Physical, Chemical and Earth Sciences, EMBiology, Reaxys
کلیدواژه ها (انگلیسی):Homology modeling , Docking , MD simulation , CCR2 , Inflammation , INCB3344
Subjects:QV pharmacology > QV 744 Medicinal Chemistry
QV pharmacology
Divisions:School of Pharmacy > Department of Medicinal Chemistry
ID Code:8443
Deposited By: Mrs sepideh Dashti
Deposited On:05 Nov 1395 09:16
Last Modified:12 Dec 1396 08:03

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