Tropical Journal of Pharmaceutical Research
Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, Nigeria
Vol. 14, No. 12, 2015, pp. 2171-2178
Bioline Code: pr15285
Full paper language: English
Document type: Research Article
Document available free of charge
Tropical Journal of Pharmaceutical Research, Vol. 14, No. 12, 2015, pp. 2171-2178
© Copyright 2015 - Tropical Journal of Pharmaceutical Research
Structural and Dynamic Insight into Hirudin Epitopes-HLADRB1 0101 Complexes and their Modified Peptide Ligands: A Molecular Dynamic Simulation Study|
Asgari, Saeme; Mirzahoseini, Hasan; Karimipour, Morteza & Ebrahim-Habibi, Azadeh
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.
Result: 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.
Modified peptide ligand; Epitopes; MHC peptide binding; Hirudin; Modified peptide ligands; Molecular dynamic simulation; Binding free energy
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