Saeme Asgari1,
Hasan Mirzahoseini2
,
Morteza Karimipour3,
Azadeh Ebrahim-Habibi4,5
1Department of Biology, Science and Research Branch, Islamic Azad University;
2Medical Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran;
3Molecular Medicine Department, Biotechnology Research Center, Pasteur Institute of Iran;
4Biosensor Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute;
5Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
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] Hir1-15 and [Gly9] Hir1-15, [Gly21] Hir13-27 and [Lys21] Hir13-27. 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