In silico Study of the interaction of fucoidan with thrombolytic agents

Abstract

Background: Tissue plasminogen activator (tPA) is one of the most widely used drugs in thrombolytic therapy. However, due to the inactivation of tPA in the bloodstream and increased risk of bleeding with increasing tPA dosages, the development of targeted delivery systems of tPA is required. For these purposes, it is possible to use fucoidan. The aim of the work was to study the possibility of forming of tPA-fucoidan conjugates and maintaining the activity of the enzyme using molecular docking. Methods: Docking simulations between tPA and fucoidan were performed by use of a docking software AutoDock tools version 1.5.7 and AutoDock 4.2.6. Using “blind docking” to identify the centers of molecular docking approaches of the enzyme (tPA) with the ligand (the active part of the fucoidan structure), as well as to establish the influence of the ligand on the active site of the enzyme. Results: Two “hot spots” of fucoidan binding to the enzyme were found: the region containing SER85-CYS97 residues and the region containing PHE217-TYR223 residues. This interaction can lead to the successful binding of the enzyme and polysaccharide to form a protein-polysaccharide complex. In this case, there may be a lack of suppression of the action of tPA. The interaction with the ligand was found to occur on the surface of the protein molecule. Conclusions: In this study, coupling simulations of interactions of tPA with fucoidan were conducted. The resulting conjugate can be used in the development of systems for the targeted delivery of a thrombolytic agent. This study predicts that the formation of tPA-fucoidan conjugate is a promising approach for optimizing treatment strategies for thrombosis.