Molecular docking and dynamics simulation analysis of the human FXIIa with compounds from the Mcule database

Abstract

The human factor XIIa is a serine protease enzyme that is implicated in the pathological thrombosis. This coagulation factor represents an interesting molecular target to design safer antithrombotic agents without adversely influencing physiological hemostasis. Therefore, it is of interest to virtually screen the human factor XIIa crystal with millions of compounds in Mcule database in order to identify potential inhibitors. For this purpose, both molecular docking and dynamics simulation were employed to identify potential hits. Also, various predictive approaches were utilized to estimate chemical, pharmacokinetics and toxicological features for the top hits. As such, we report here that compound 4 (1‐(4‐benzylpiperazin‐1‐yl)‐2‐[5‐(3,5‐dimethylpyrazol‐1‐yl)‐1,2,3,4‐tetrazol‐2‐yl]ethanone) may be a potential ligand against the human factor XIIa for further consideration in the design and development of novel antithrombotic agents.