Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Structural and dynamic insight into Hirudin epitopes-HLA-DRB1 0101 complexes and their modified peptide ligands: A molecular dynamic simulation study

Saeme Asgari¹, Hasan Mirzahoseini² , Morteza Karimipour³, Azadeh Ebrahim-Habibi^4,5

For correspondence:- Hasan Mirzahoseini Email: mirzahoseini@pasteur.ac.ir Tel:+982166057220

Received: 6 July 2015 Accepted: 26 October 2015 Published: 27 December 2015

Citation: Asgari S, Mirzahoseini H, Karimipour M, Ebrahim-Habibi A. Structural and dynamic insight into Hirudin epitopes-HLA-DRB1 0101 complexes and their modified peptide ligands: A molecular dynamic simulation study. Trop J Pharm Res 2015; 14(12):2171-2178 doi: 10.4314/tjpr.v14i12.3

© 2015 The authors.
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Abstract

Purpose: To develop a hirudin therapeutic protein that eliminates unwanted immune response.

Methods: Molecular dynamic simulation was performed on immunodominant hirudin epitopes 1-15 and 13-27 and its analog, modified peptide ligands (MPLs), namely, [Lys⁴] Hir_1-15 and [Gly⁹] Hir_1-15, [Gly²¹] Hir_13-27 and [Lys²¹] Hir_13-27. The selected epitopes were modeled and 20 ns of molecular dynamics simulation was performed on peptide-HLA1 0101 and MPLs-HLA1 0101 complexes to gain a better understanding of molecular recognition mechanisms of MHC peptide binding. Characterization of the process was done by evaluation of root mean square deviation (RMSD) and total energy of binding.

Results: All complexes of MPLs-HLA-DRB1 0101 showed thermodynamically unstable structure in comparison with native epitopes-HLA-DRB1 0101. The findings indicate that these analogs have different orientation in HLA grooves and are not available for suitable interaction with HLA-DRB1 0101.

Conclusion: Altogether, the results show the potentials of predictive methods and molecular modeling in molecular mimicry of peptide-MHC interaction and provide insights into the binding characteristics of antigen presentation mechanism.

Keywords: Modified peptide ligand, Epitopes, MHC peptide binding, Hirudin, Modified peptide ligands, Molecular dynamic simulation, Binding free energy