In silico identification of mimicking molecule(s) triggering von Willebrand factor in human: a molecular drug target for regulating coagulation pathway.

Blood coagulation is a complex and dynamic process wherein the body activates its emergency mechanism to stop bleeding and wound healing via the interactions of prothrombotic and antithrombotic agents. von Willebrand factor (VWF) is a complex glycoprotein and initial component of the hemostasis pathway which serves a multipurpose role in blood coagulation process. There are reports of various plants that contain several bioactive compounds possessing properties of inducing blood coagulation directly or indirectly. In the present study, efforts have been made to identify bioactive compounds that may play a significant role in regulation of the coagulation cascade by accelerating VWF and thus enhance the hemostasis process. An antidiuretic peptide drug, Desmopressin, works on VWF and releases them in circulation. Forty-seven compounds from different plant sources were screened through molecular docking, out of which two compounds, Emodin and Peruvianoside II, showed more binding affinity than the reference drug Desmopressin. Emodin and Peruvianoside II showed binding energies -7.2 and -7.0 kcal/mol, respectively, when docked with VWF, whereas Desmopressin displayed less binding energy (-6.9 kcal/mol). Emodin belongs to anthraquinone from Rumex hastasus and Peruvianoside II belongs to flavanone glycosides from Thevetia peruviana. The mimicking potential of top identified molecules with respect to the drug was confirmed through simulation analysis. Besides, the molecular dynamics simulation (MDS) study (for 20 ns) showed that the Peruvianoside II protein complex was energetically more stable than Emodin protein complex. Based on the results, Peruvianoside II possesses great potential and thus may be considered for development of drugs for hemostasis. Communicated by Ramaswamy H. Sarma.