How to explore and exploit blood coagulation mechanisms using an in silico approach
According to the materials of report at the meeting of the Presidium of the NAS of Ukraine, October 30, 2024
DOI:
https://doi.org/10.15407/visn2024.12.088Keywords:
blood circulation, thrombosis, bleeding, fibrin, peptides, prothrombin, molecular docking.Abstract
This study explores the use of in silico methods for developing novel therapeutic compounds, showcasing the design of a prototype antithrombotic drug based on peptide mimetics from the superspiral region of the fibrin(ogen) molecule. Functional sites on the molecule were identified in silico, leading to the selection of peptide sequences that were subsequently synthesized and tested. In vitro studies confirmed the peptides’ potent inhibitory effects on fibrin polymerization. Additionally, docking and molecular dynamics simulations were employed to model derivatives of the N-terminal fragment of staphylocoagulase, known for its capacity to non-enzymatically activate prothrombin. The continuation of these approaches holds significant potential for the development of both novel antithrombotic agents and unique blood coagulation activators for rapid hemorrhage control.
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