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

Area of Science:

• Biochemistry
• Pharmacology
• Computational Chemistry

Background:

• Human factor XIIa (FXIIa) is a serine protease linked to pathological thrombosis.
• FXIIa is a potential target for developing antithrombotic drugs with improved safety profiles.
• Targeting FXIIa may offer anticoagulation without disrupting normal hemostasis.

Purpose of the Study:

• To virtually screen a large compound library against human FXIIa.
• To identify potential FXIIa inhibitors for novel antithrombotic agent development.
• To evaluate the properties of identified hit compounds.

Main Methods:

• Molecular docking and dynamics simulations were used to screen millions of compounds.
• Virtual screening was performed against the human FXIIa crystal structure.
• Predictive computational approaches assessed chemical, pharmacokinetic, and toxicological features of top hits.

Main Results:

• Compound 4 (1-(4-benzylpiperazin-1-yl)-2-[5-(3,5-dimethylpyrazol-1-yl)-1,2,3, 4-tetrazol-2-yl]ethanone) was identified as a potential inhibitor.
• The study identified potential ligands for human FXIIa.
• Compound 4 exhibited favorable predicted properties for further development.

Conclusions:

• Compound 4 is a promising candidate for a novel antithrombotic agent targeting FXIIa.
• Further research and development are warranted for this compound.
• This study highlights the utility of virtual screening in drug discovery for thrombosis.