Isfahan University of Medical Sciences

Science Communicator Platform

Stay connected! Follow us on X network (Twitter):
Share this content! On (X network) By
Molecular Dynamics Simulation of Chemokine Receptors in Lipid Bilayer: A Case Study on C-C Chemokine Receptor Type 2 Publisher Pubmed



Shahlaei M1 ; Fassihi A2 ; Papaleo E3 ; Pourfarzam M4
Authors
Show Affiliations
Authors Affiliations
  1. 1. Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
  2. 2. Department of Medicinal Chemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, 81746-73461, Iran
  3. 3. Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, 20126, Piazza della Scienza 2, Italy
  4. 4. Department of Clinical Biochemistry, Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran

Source: Chemical Biology and Drug Design Published:2013


Abstract

Chemokine receptors belong to the membrane proteins that are included in many physiological phenomena. However, the mechanism of their action is unknown at the atomistic level in different aspects. In this study, a computational pipeline is exploited to investigate the molecular basis of how the structure of C-C chemokine receptor type 2, a prototypical chemokine receptor, is affected by lipid bilayer and an antagonist (INCB3344). This study includes homology modeling, molecular dynamics simulation in lipid bilayer, and docking. A detailed mechanism of INCB3344 has been described. Tyr 49, Trp 98, Tyr 120, His 121, and Glu 291 are proved to play important roles in binding. Integrating results obtained in this study and experimental data help us to suggest a two-step ligand-binding mechanism. The N-terminus of protein first sticks out from the extracellular domain suitable for the contact with the antagonist. Binding of ligand to this segment leads to the geometrical changes to facilitate the ligand interactions with extracellular loop 2 of C-C chemokine receptor type 2. Finally, the interactions occurring between extracellular loop 2 and ligand induce conformational changes in C-C chemokine receptor type 2 structure. These changes bring the ligand closer to the binding pocket, allowing the interaction between INCB3344 and the residues of active site. In this study, a computational pipeline is exploited to investigate the molecular basis of how the structure of C-C chemokine receptor type 2 is affected by lipid bilayer and antagonist (INCB3344) explicitly. © 2013 John Wiley & Sons A/S.
Related Docs
View other Related Docs
1. Exploring a Model of a Chemokine Receptor/Ligand Complex in an Explicit Membrane Environment by Molecular Dynamics Simulation: The Human Ccr1 Receptor, Journal of Chemical Information and Modeling (2011)
2. Homology Modeling of Human Ccr5 and Analysis of Its Binding Properties Through Molecular Docking and Molecular Dynamics Simulation, Biochimica et Biophysica Acta - Biomembranes (2011)
3. Insights Into the Human A1 Adenosine Receptor From Molecular Dynamics Simulation: Structural Study in the Presence of Lipid Membrane, Medicinal Chemistry Research (2015)
4. Characterization of Adenosine Receptor in Its Native Environment: Insights From Molecular Dynamics Simulations of Palmitoylated/Glycosylated, Membrane-Integrated Human A2b Adenosine Receptor, Journal of Molecular Modeling (2012)
5. Molecular Modeling, Structure Activity Relationship and Immunomodulatory Properties of Some Lupeol Derivatives, Medicinal Chemistry Research (2013)
6. Design of a Novel Metal Binding Peptide by Molecular Dynamics Simulation to Sequester Cu and Zn Ions, Research in Pharmaceutical Sciences (2014)
7. Discovery of Novel Rarα Agonists Using Pharmacophore-Based Virtual Screening, Molecular Docking, and Molecular Dynamics Simulation Studies, PLoS ONE (2023)
8. Preparing a Database of Corrected Protein Structures Important in Cell Signaling Pathways, Research in Pharmaceutical Sciences (2023)
Experts (# of related papers)
View all Related Experts
Afshin Fassihi (23)
Lotfollah Saghaie Dehkordi (15)
Other Related Docs
9. Comparison of Epothilone and Taxol Binding in Yeast Tubulin Using Molecular Modeling, Avicenna Journal of Medical Biotechnology (2011)
10. Qsar Study of Some Ccr5 Antagonists As Anti-Hiv Agents Using Radial Basis Function Neural Network and General Regression Neural Network on the Basis of Principal Components, Medicinal Chemistry Research (2012)
11. Application of an Expert System Based on Genetic Algorithm-Adaptive Neuro-Fuzzy Inference System (Ga-Anfis) in Qsar of Cathepsin K Inhibitors, Expert Systems with Applications (2012)
12. Statistically Validated Qsar Study of Some Antagonists of the Human Ccr5 Receptor Using Least Square Support Vector Machine Based on the Genetic Algorithm and Factor Analysis, Medicinal Chemistry Research (2013)
13. Damage Intensity of Carvacrol on Prostatic Cancer Cells Linedu145 and Molecular Dynamic Simulation of It Effect on Apoptotic Factors, International Journal of PharmTech Research (2016)
14. Gp41 Inhibitory Activity Prediction of Theaflavin Derivatives Using Ligand/Structure-Based Virtual Screening Approaches, Computational Biology and Chemistry (2019)
15. Integrating Docking and Molecular Dynamics Approaches for a Series of Proline-Based 2,5-Diketopiperazines As Novel Αβ-Tubulin Inhibitors, Journal of Biomolecular Structure and Dynamics (2015)
16. Theoretical Design of a New Chimeric Protein for the Treatment of Breast Cancer, Research in Pharmaceutical Sciences (2016)
17. Exploring the Interaction Between Epidermal Growth Factor Receptor Tyrosine Kinase and Some of the Synthesized Inhibitors Using Combination of In-Silico and In-Vitro Cytotoxicity Methods, Research in Pharmaceutical Sciences (2018)
18. Rational Design of a New Mutant of Tobacco Etch Virus Protease in Order to Increase the in Vitro Solubility, Research in Pharmaceutical Sciences (2020)
19. A Modeling Study of Aldehyde Inhibitors of Human Cathepsin K Using Partial Least Squares Method, Research in Pharmaceutical Sciences (2011)
20. Qsar Analysis of Some 1-(3,3-Diphenylpropyl)-Piperidinyl Amides and Ureas As Ccr5 Inhibitors Using Genetic Algorithm-Least Square Support Vector Machine, Medicinal Chemistry Research (2013)
21. Novel 9-(Alkylthio)-Acenaphtho[1,2-E]-1,2,4-Triazine Derivatives: Synthesis, Cytotoxic Activity and Molecular Docking Studies on B-Cell Lymphoma 2 (Bcl-2), DARU, Journal of Pharmaceutical Sciences (2014)
22. Therapeutic Targeting of Chemokines and Chemokine Receptors in Multiple Sclerosis: Opportunities and Challenges, CNS and Neurological Disorders - Drug Targets (2018)
23. Evaluation of Humoral and Cellular Immune Responses Against Vibrio Cholerae Using Oral Immunization by Multi-Epitope-Phage-Based Vaccine, International Immunopharmacology (2024)
24. Elucidation of Molecular Mechanisms Behind the Self-Assembly Behavior of Chitosan Amphiphilic Derivatives Through Experiment and Molecular Modeling, Pharmaceutical Research (2015)
25. Novel 2-Alkylthio-1-Benzylimidazole-5-Carboxylic Acid Derivatives Targeting Gp41: Design, Synthesis, and in Vitro Anti-Hiv Activity Evaluation, Current HIV Research (2022)
26. In-Silico Design of a New Multi-Epitope Vaccine Candidate Against Sars-Cov-2, Acta Virologica (2023)
27. Qsar Study of Some 5-Methyl/Trifluoromethoxy-1H-Indole-2,3-Dione-3- Thiosemicarbazone Derivatives As Anti-Tubercular Agents, Research in Pharmaceutical Sciences (2009)
28. The Interaction of a New Schiff Base Ligand With Human Serum Albumin: Molecular Docking and Molecular Dynamics Simulation Studies, Journal of Macromolecular Science, Part B: Physics (2017)
29. Prediction of P38 Map Kinase Inhibitory Activity of 3, 4-Dihydropyrido [3, 2-D] Pyrimidone Derivatives Using an Expert System Based on Principal Component Analysis and Least Square Support Vector Machine, Research in Pharmaceutical Sciences (2014)
30. New Heat Shock Protein (Hsp90) Inhibitors, Designed by Pharmacophore Modeling and Virtual Screening: Synthesis, Biological Evaluation and Molecular Dynamics Studies, Journal of Biomolecular Structure and Dynamics (2020)
31. Virtual Screening of M3 Protein Antagonists for Finding a Model to Study the Gammaherpesvirus Damaged Immune System and Chemokine Related Diseases, BioImpacts (2013)
32. A Qsar Study of Some Cyclobutenediones As Ccr1 Antagonists by Artificial Neural Networks Based on Principal Component Analysis, DARU, Journal of Pharmaceutical Sciences (2011)
33. Molecular Modelling Study on Pyrrolo[2,3-B]Pyridine Derivatives As C-Met Kinase Inhibitors: A Combined Approach Using Molecular Docking, 3D-Qsar Modelling and Molecular Dynamics Simulation, Molecular Simulation (2020)
34. Qsar Analysis for Some Diaryl-Substituted Pyrazoles As Ccr2 Inhibitors by Ga-Stepwise Mlr, Chemical Biology and Drug Design (2011)
35. Computational Design of Tryprostatin-A Derivatives As Novel Ββ-Tubulin Inhibitors, Journal of Biomolecular Structure and Dynamics (2015)
36. In Silico Screening for Novel Tyrosine Kinase Inhibitors With Oxindole Scaffold As Anti-Cancer Agents: Design, Qsar Analysis, Molecular Docking and Admet Studies, Journal of Computational Biophysics and Chemistry (2022)
37. Hiv-1 Entry Inhibitors: A Review of Experimental and Computational Studies, Chemistry and Biodiversity (2018)
38. Synthesis, Molecular Docking and Molecular Dynamics Simulation of 2- Thioxothiazolidin-4-One Derivatives Against Gp41, Current HIV Research (2020)
39. 3D-Qsar, Molecular Docking, and Molecular Dynamic Simulations for Prediction of New Hsp90 Inhibitors Based on Isoxazole Scaffold, Journal of Biomolecular Structure and Dynamics (2018)
40. Bioinformatic Analysis of Different Fusions of Ipad, Pa20 and Ctxb Antigens: A Preliminary Analysis for Vaccine Design, Genetics in the Third Millennium (2016)
41. Design and Synthesis of Novel Phe-Phe Hydroxyethylene Derivatives As Potential Coronavirus Main Protease Inhibitors, Journal of Biomolecular Structure and Dynamics (2022)
42. Quantitative Structure Activities Relationships of Some 2-Mercaptoimidazoles As Ccr2 Inhibitors Using Genetic Algorithm-Artificial Neural Networks, Research in Pharmaceutical Sciences (2013)
43. Identification of New Hsp90 Inhibitors: Structure Based Virtual Screening, Molecular Dynamic Simulation, Synthesis and Biological Evaluation, Anti-Cancer Agents in Medicinal Chemistry (2021)
44. Computational Evaluation of Some Indenopyrazole Derivatives As Anticancer Compounds; Application of Qsar and Docking Methodologies, Journal of Enzyme Inhibition and Medicinal Chemistry (2013)
45. An In-Silico Screening Strategy to the Prediction of New Inhibitors of Covid-19 Mpro Protein, Iranian Journal of Pharmaceutical Research (2021)