Structure prediction of GPCRs using piecewise homologs and application to the human CCR5 chemokine receptor: validation through agonist and antagonist docking

Journal of Biomolecular Structure & Dynamics
Karthik ArumugamJean-Claude Schmit


This article describes the construction and validation of a three-dimensional model of the human CC chemokine receptor 5 (CCR5) receptor using multiple homology modeling. A new methodology is presented where we built each secondary structural model of the protein separately from distantly related homologs of known structure. The reliability of our approach for G-protein coupled receptors was assessed through the building of the human C-X-C chemokine receptor type 4 (CXCR4) receptor of known crystal structure. The models are refined using molecular dynamics simulations and energy minimizations using CHARMM, a classical force field for proteins. Finally, docking models of both the natural agonists and the antagonists of the receptors CCR5 and CXCR4 are proposed. This study explores the possible binding process of ligands to the receptor cavity of chemokine receptors at molecular and atomic levels. We proposed few crucial residues in receptors binding to agonist/antagonist for further validation through experimental analysis. In particular, our study provides better understanding of the blockage mechanism of the chemokine receptors CCR5 and CXCR4, and may help the identification of new lead compounds for drug development in HIV in...Continue Reading


Mar 22, 2014·International Journal of Molecular Sciences·Inger LindinIngebrigt Sylte
Apr 25, 2014·The AAPS Journal·Wan-Gang GuJun-Fa Yuan
Apr 23, 2016·Future Medicinal Chemistry·Samuel A McKie
Sep 4, 2014·Science Signaling·Martyna SzpakowskaAndy Chevigne
Jul 22, 2018·Chemistry & Biodiversity·Tahereh Mostashari RadAfshin Fassihi


Jan 1, 1994·Annual Review of Immunology·P M Murphy
Dec 5, 1993·Journal of Molecular Biology·A Sali, T L Blundell
Feb 1, 1996·Journal of Molecular Graphics·W HumphreyK Schulten
Dec 6, 1996·The Journal of Biological Chemistry·L WuS Qin
Sep 30, 1998·Proceedings of the National Academy of Sciences of the United States of America·A KinterA S Fauci
Apr 8, 2000·Current Opinion in Structural Biology·T Lazaridis, M Karplus
Apr 26, 2000·Proceedings of the National Academy of Sciences of the United States of America·T DragicJ P Moore
Jun 27, 2000·Bioinformatics·L J McGuffinD T Jones
Jan 12, 2001·Journal of Molecular Biology·Anders KroghErik L L Sonnhammer
Mar 29, 2001·Nature Immunology·C R Mackay
Mar 29, 2001·Nature Immunology·C Gerard, B J Rollins
Mar 29, 2001·Nature Immunology·B Moser, P Loetscher
Oct 9, 2001·Bioinformatics·G E Tusnády, Istvan Simon
Jun 28, 2002·Journal of Chemical Information and Computer Sciences·Davor JuretićDamir Zucić
Nov 29, 2002·Protein Engineering·Miklos CserzöIstvan Simon
Jan 14, 2003·Biophysical Journal·Xiaoqin HuangKaixian Chen
Feb 13, 2003·Journal of the American Chemical Society·Cyril DominguezAlexandre M J J Bonvin
Sep 6, 2003·The Journal of Biological Chemistry·John O TrentStephen C Peiper
Aug 26, 2004·Journal of Molecular Biology·Tetsuji OkadaVolker Buss
Dec 31, 2005·Nucleic Acids Research·David S WishartJennifer Woolsey
Oct 26, 2007·European Biophysics Journal : EBJ·Anthony Ivetac, Mark S P Sansom
Dec 22, 2007·Molecular Pharmacology·Rama KondruMarianna Dioszegi
May 16, 2008·Nature·Midori Murakami, Tsutomu Kouyama
Jul 3, 2008·Nature·Tony WarneGebhard F X Schertler
Apr 29, 2009·Journal of Computational Chemistry·Garrett M MorrisArthur J Olson
Jun 25, 2009·Protein Science : a Publication of the Protein Society·Christopher T VeldkampBrian F Volkman
Oct 21, 2010·Journal of Computer-aided Molecular Design·Marco A C NevesM Luisa Sá e Melo
May 5, 2011·Journal of Computational Chemistry·Aurélien GrosdidierOlivier Michielin

Related Concepts

CCR5 Receptor Antagonists
Drug Development
Molecular Dynamics
CXCR4 gene
Antagonist Muscle Action
Homology Modeling
C-X-C Motif Chemokine 12 Receptor Activity
HIV Infections
Body Cavities

Trending Feeds


Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Synapse Loss as Therapeutic Target in MS

As we age, the number of synapses present in the human brain starts to decline, but in neurodegenerative diseases this occurs at an accelerated rate. In MS, it has been shown that there is a reduction in synaptic density, which presents a potential target for treatment. Here is the latest research on synapse loss as a therapeutic target in MS.

Artificial Intelligence in Cardiac Imaging

Artificial intelligence (ai) techniques are increasingly applied to cardiovascular (cv) medicine in cardiac imaging analysis. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

Social Learning

Social learning involves learning new behaviors through observation, imitation and modeling. Follow this feed to stay up to date on the latest research.

Cell Atlas of the Human Eye

Constructing a cell atlas of the human eye will require transcriptomic and histologic analysis over the lifespan. This understanding will aid in the study of development and disease. Find the latest research pertaining to the Cell Atlas of the Human Eye here.

Single Cell Chromatin Profiling

Techniques like ATAC-seq and CUT&Tag have the potential to allow single cell profiling of chromatin accessibility, histones, and TFs. This will provide novel insight into cellular heterogeneity and cell states. Discover the latest research on single cell chromatin profiling here.

Genetic Screens in iPSC-derived Brain Cells

Genetic screening is a critical tool that can be employed to define and understand gene function and interaction. This feed focuses on genetic screens conducted using induced pluripotent stem cell (iPSC)-derived brain cells.