In Silico Design of Novel Anticoagulant Peptides targeting Blood Coagulation Factor VIIa

Objectives:the coagulation cascade initiated during vascular injury prevents bleeding. unwanted clot formation is however detrimental and requires the use of anticoagulants for prophylaxis and treatment. anticoagulants targeting a specific step or an enzyme in the clotting process are most preferred as they minimise disadvantageous side-effects. a principal step in the discovery of novel anticoagulants encompasses the in silico design of potential leads. this study depicts the in silico design of peptide anticoagulants targeting coagulation factor viia.methods:applying the proline bracket rule and using various bioinformatics tools: the basic alignment search tool (blast) of national center for biotechnology information; the t-coffee module provided by european molecular biology laboratory-european bioinformatics institute, and several modules available on the expasy server, we designed five bivalent chimeric anticoagulants targeting factor viia, using factor viia inhibitors – hemextin a from hemachatus haemachatus (african ringhals cobra) venom and factor viia exosite-inhibitor peptide as templates. six peptides were derived from hemextin a, which were concomitantly fused with factor viia exosite-inhibitor peptide intermediated by a polyalanine spacer, and analysed for structural stability using the swiss-model software developed at the swiss institute of bioinformatics and weblab viewerpro (version 4.2).results:twelve chimeric peptides were obtained; only five exhibited stable structures in silico.conclusion:the five peptides obtained are probable anticoagulant leads that should be further evaluated using suitable in vitro and in vivo assays. further, this study shows how simple web-based modules can be used for the rational design of probable leads targeting specific physiological molecular targets.