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Molecular Diversity

, Volume 16, Issue 2, pp 401–413 | Cite as

Binding site characterization of G protein-coupled receptor by alanine-scanning mutagenesis using molecular dynamics and binding free energy approach: application to C-C chemokine receptor-2 (CCR2)

  • Swapnil Chavan
  • Shirishkumar Pawar
  • Rajesh Singh
  • M. Elizabeth Sobhia
Full-Length Paper

Abstract

The C-C chemokine receptor 2 (CCR2) was proved as a multidrug target in many diseases like diabetes, inflammation and AIDS, but rational drug design on this target is still lagging behind as the information on the exact binding site and the crystal structure is not yet available. Therefore, for a successful structure-based drug design, an accurate receptor model in ligand-bound state is necessary. In this study, binding-site residues of CCR2 was determined using in silico alanine scanning mutagenesis and the interactions between TAK-779 and the developed homology model of CCR2. Molecular dynamic simulation and Molecular Mechanics-Generalized Born Solvent Area method was applied to calculate binding free energy difference between the template and mutated protein. Upon mutating 29 amino acids of template protein and comparison of binding free energy with wild type, six residues were identified as putative hot spots of CCR2.

Keywords

CCR2 In silico alanine scanning mutagenesis Molecular dynamics Hot spots MM-GBSA 

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Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  • Swapnil Chavan
    • 1
  • Shirishkumar Pawar
    • 1
  • Rajesh Singh
    • 1
  • M. Elizabeth Sobhia
    • 1
  1. 1.Department of PharmacoinformaticsNational Institute of Pharmaceutical Education and ResearchS.A.S. NagarIndia

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