IN SILICO STUDY OF ALBENDAZOLE MOLECULAR DOCKING WITH VEGFR-2

Аннотация

This study investigates the molecular docking of albendazole with Vascular Endothelial Growth Factor Receptor-2 (VEGFR-2), a key protein involved in tumor angiogenesis. The results revealed multiple binding poses, with the most stable interaction showing a Vina score of -6.8 kcal/mol, indicating a strong ligand-receptor complex. These findings support albendazole’s potential role in targeting VEGFR-2-mediated pathways, reinforcing its relevance in cancer research. Keywords: Albendazole, Molecular Docking, VEGFR-2, AutoDock Vina, Angiogenesis, Anti- Cancer Activity, Benzimidazole, Ligand-Receptor Interaction, Computational Chemistry, Drug Repurposing. Molecular docking studies of benzimidazole derivatives have gained attention due to their diverse biological activities and potential therapeutic applications. Albendazole, a benzimidazole derivative, primarily exerts its pharmacological effects by binding to β-tubulin, thereby inhibiting microtubule polymerization. This mode of action has been supported by several studies, including one where researchers utilized molecular docking to identify binding sites and affinities of albendazole and its derivatives against mutant and wild-type tubulin structures. This study indicated that albendazole possesses a robust binding affinity that varied depending on the mutations present in tubulin [1.252 p.]. Additionally, albendazole has been shown to disrupt microtubule function, causing cytotoxicity in tumor cells, thereby broadening its therapeutic implications to include anti-cancer activity [2.877 p.]. Vascular Endothelial Growth Factor Receptor-2 (VEGFR-2) plays a pivotal role in tumor angiogenesis, facilitating the formation of new blood vessels that supply nutrients and oxygen to tumors, thereby promoting their growth and potential metastasis. Overexpression of VEGFR-2 has been observed in various cancers, including gastric and ovarian cancers, and is associated with poor prognosis and increased tumor aggressiveness [3.2 p.]. Molecular docking studies of albendazole has conducted using human Vascular endothelial growth factor receptor-2 (VEGFR-2 kinase receptor) protein (PDB ID: 3VHE). The protein was obtained from “Protein data bank” and prepared using Pymol software. Intrinsic water molecules had removed from protein’s pocket area and polar hydrogens are inserted. Struture of albendazole is obtained from Pubchem database. AM1 semi-empirical force fields were used to optimize the ligand structure and converted into pdb format. This research aims to shed insight on the binding properties of 3VHE protein using geometrically optimized chemicals like ABZ. Before being employed in molecular interaction 107 RESPUBLIKA ILMIY-AMALIY KONFERENSIYASI 7-8-MAY 2025-YIL studies, proteins were checked for missing side-chain residues using the open Molecular Mechanics (MM) simulation tool. Autodock v 4.2.6 was used for molecular docking investigations. Vina Coorinates Cavity Active binding sites Score (x,y,z) volume (kcal/mol) (A3) -6.8 1, 31, 16 212 Chain A: LEU21 ARG23 VAL25 ALA43 LYS45 GLU58 VAL72 VAL87 VAL89 GLU90 PHE91 CYS92 LYS93 PHE94 GLY95 ASN96 ASP142 ARG146 ASN147 LEU149 CYS159 PHE161 -6.0 10, 32, 3 144 Chain A: SER6 LYS7 TRP8 GLU9 PHE10 PRO11 ARG14 GLY32 ILE33 ASP34 LYS35 LEU62 GLY66 HIS67 ASN73 LEU74 LEU75 GLY76 LYS80 GLU90 -5.7 2, 43, 17 221 Chain A: ARG23 VAL25 ALA43 VAL44 LYS45 LEU47 GLU51 ALA54 LEU55 GLU58 ILE61 LEU62 HIS64 ILE65 VAL72 VAL87 ILE88 VAL89 ASN96 LEU133 LYS137 CYS138 ILE139 HIS140 ARG141 ASP142 ARG146 ASN147 LEU149 CYS159 ASP160 PHE161 PRO162 TYR176 -5.3 10, 27, 12 145 Chain A: GLU27 ILE33 ASP34 CYS39 ARG40 THR41 VAL42 HIS67 LEU69 ASN73 LEU74 LEU75 VAL89 GLU90 PHE91 CYS92 LYS93 SER151 GLU152 LYS153 VAL155 LYS157 Table-1. Vina scores coordinates, cavity volumes and active binding sites of albendazole in with VEGFR-2 receptor protein in different poses. In Table 1, we can see that a blind docking analysis was performed using Autodock, in which albendazole is located in four different poses in the protein cavity. The first column of the table presents the Vina scores. The smaller the negative value of the Vina score, the higher the protein- ligand bond strength, and the ligand and protein have a strong interaction in this pose. If we look at the table, we can see that the Vina scores range from -6.8 to -5.3. The smallest Vina score is -6.8, which shows the strongest ligand-protein binding in this pose. The second column of the table presents the coordinates of the ligand in different poses within the protein cavity. The third column presents the volumes of the protein cavity. The fourth column presents the active binding sites of the ligand and the protein amino acids. In Figure 1, we can see the binding of the most stable pose in the protein cavity and the active binding site. Figure-1. Active binding site of the most stable pose of albendazole and its view in VEGFR-2 108 “TABIIY FANLAR: DOLZARB MUAMMOLAR VA ULARNING YECHIMLARI” receptor protein cavity