Identification of selective ligands for human fibrin recognition using high-throughput docking

Area of Science:

• Biochemistry
• Nanotechnology
• Pharmacology

Background:

• Polymerized fibrin is the primary component of thrombi (blood clots).
• Targeted drug delivery nanoparticles can mitigate systemic side effects of fibrinolytic drugs.
• Identifying specific ligands for fibrin is crucial for developing effective targeted therapies.

Purpose of the Study:

• To discover novel molecules that selectively recognize polymerized human fibrin.
• To identify potential ligands for targeted delivery of fibrinolytic agents via nanoparticles.
• To validate a computational and experimental approach for finding fibrin-binding compounds.

Main Methods:

• High-throughput molecular docking was employed to screen a large library of commercial compounds.
• Compounds were screened for their potential interaction with the human fibrin γ(312-324) epitope.
• Fluorimetric assays were used to determine the binding affinity of selected compounds to fibrin.

Main Results:

• A computational screening protocol successfully identified potential fibrin-recognizing molecules.
• Selected compounds demonstrated varying degrees of affinity for fibrin in experimental assays.
• The study validated the proposed method for discovering lead molecules for fibrin recognition.

Conclusions:

• The developed protocol offers a valuable approach for identifying novel compounds that bind to human fibrin.
• These findings contribute to the development of targeted therapies for thrombotic disorders.
• The identified molecules show promise as ligands for nanoparticle-based drug delivery systems.