Research Article Open Access

HOMOLOGY MODELING AND MOLECULAR DYNAMICS STUDIES OF EC1 DOMAIN OF VE-CADHERIN TO ELUCIDATE DOCKING INTERACTION WITH CADHERIN-DERIVED PEPTIDE

Vivitri Dewi Prasasty1, Usman Sumo Friend Tambunan1 and Teruna Jaya Siahaan2
  • 1 University of Indonesia, Indonesia
  • 2 The University of Kansas, United States

Abstract

VE-cadherin is a protein in the cadherin family that is found at the adherens junctions of the microvessel endothelial cells of the Blood-Brain Barrier (BBB). It is recognized as the homotypic cell adhesion molecules and there is limited structural information on how VE-cadherins mediate cell-cell adhesion. It has been shown that the EC1 domain of cadherins is important for the homophilic interactions for cell-cell adhesion. Therefore, the aims of this study are to model the structure of the EC1 domain of VE-cadherin, study its molecular dynamics properties and evaluate its interactions with cadherin peptides. In this study, the sequence alignment between EC1 domain of VE-cadherin and the template protein were conducted by CLUSTALW2 platform. The SWISS-MODEL platform performed the homology modeling of the EC1 domain of VE-cadherin structure. Structural refinement was done by using KOBAMIN. Some validation analysis platforms also were conducted included PROCHECK, VERIFY3D, ERRAT and MOLPROBITY to check the allowed residues region in Ramachandran Plot (RP) and the quality of the structure. The most favored region was found 95.5% in RP value and overall model structure quality is 71.34%. Molecular Dynamics (MD) was run under CABS-FLEX to determine the flexibility of the residue index. The RMSD value of MD is 1.5Å per residue index. Eventually, molecular docking by AUTODOCK VINA was conducted to investigate protein-ligand interaction. From docking, it is found that the affinity energy is -4.8 kcal/mol which has the most favorable binding of EC1 domain with the peptide.

OnLine Journal of Biological Sciences
Volume 14 No. 2, 2014, 155-162

DOI: https://doi.org/10.3844/ojbsci.2014.155.162

Submitted On: 23 May 2014 Published On: 25 June 2014

How to Cite: Prasasty, V. D., Tambunan, U. S. F. & Siahaan, T. J. (2014). HOMOLOGY MODELING AND MOLECULAR DYNAMICS STUDIES OF EC1 DOMAIN OF VE-CADHERIN TO ELUCIDATE DOCKING INTERACTION WITH CADHERIN-DERIVED PEPTIDE. OnLine Journal of Biological Sciences, 14(2), 155-162. https://doi.org/10.3844/ojbsci.2014.155.162

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Keywords

  • VE-Cadherin
  • Blood Brain Barrier
  • Homology Modeling
  • Molecular Dynamics
  • Molecular Docking