Structure Based Docking of Small Hirudin like Peptides with Thrombin

Abstract

Hirudin variant like small peptide or peptidomemitic compounds are known to inhibit thrombin. These 10 to 20 amino acid long molecules are reported to primarily bind at exosite 1 of thrombin. To know more about their interaction with thrombin, initially we docked 5 different hirudin variant peptides having 10 to 13 aa sequences. It helped to identify single best docking peptide (12 aa sequence) i.e. GDFEEIPEEYLQ (pdb: 1FPH _I chain) with docking score -3.42 kcal/Mol, amongst the set of peptides. This peptide was further truncated to form a series of peptides having 7 to 12 aa sequence range. The truncated peptides were further docked at thrombin exosite 1 binding site. Amongst these the best docking 7 aa peptide i.e. GDFEEIP, with docking score -4.43 kcal/Mol was identified. This experiment helped to predict the best possible peptide sequence, much needed for strong thrombin docking and can be competent peptide based antithrombin lead.