MIXED-LIGAND COMPLEX OF COBALT WITH GLUTARIC ACID AND NICOTINAMIDE (CoGANA) MOLECULAR DOCKING ANALYSIS

401 Volume 5, Issue 10: Special Issue (EJAR) ISSN: 2181-2020 MPHAPP THE 6TH INTERNATIONAL SCIENTIFIC AND PRACTICAL CONFERENCE “MODERN PHARMACEUTICS: ACTUAL PROBLEMS AND PROSPECTS” TASHKENT, OCTOBER 17, 2025 in-academy.uz MIXED-LIGAND COMPLEX OF COBALT WITH GLUTARIC ACID AND NICOTINAMIDE (CoGANA) MOLECULAR DOCKING ANALYSIS G’oyibnazarova M.A. Pulatova G.U. Fatxullayeva M. Jumabaev F.R. Tashkent Pharmaceutical Institute, Uzbekistan e-mail: [email protected], phone: +99894-695-52-25 https://doi.org/10.5281/zenodo.17340327 Relevance: Glutaric acid (pentanedioic acid) is an aliphatic organic compound used as a raw material in the synthesis of anticancer drugs and antibiotics, pharmaceutical and chemical products, as well as a model compound for understanding metabolic disorders and hereditary enzyme deficiencies. Cobalt, being a component of vitamin B12, forms complexes, and its deficiency leads to anemia. Therefore, the synthesis of a complex compound involving glutaric acid, nicotinamide, and cobalt, followed by an analysis of its physicochemical and pharmacokinetic properties, is an important research task. Objective of the study: To determine, from the perspective of energy efficiency, the most stable conformations of the mixed-ligand cobalt complex with glutaric acid and nicotinamide (CoGANA) when interacting with target proteins. Materials and methods: The molecular docking analysis of the CoGANA molecule was carried out using Biovia DS Visualizer software and the CB-Dock 2 web server. Results and discussion: Molecular docking is one of the main in silico research methods, enabling the development of new and effective drugs. At the beginning of our study, protein structures with the following PDB ID numbers: 1SCZ, 3WD0, 4LEP, 5RVW, 5RVX, 5RVY, 5RVZ, 5RVW1, 5RVW0, and 6SV1 were downloaded in .pdb format from the Protein Data Bank (PDB) (https://www.rcsb.org/). Afterward, the binding efficiency of CoGANA with these proteins and the formation of stable conformations were determined. For this, water molecules and heteroatoms, particularly existing ligands, were removed from the protein structures using Biovia DS Visualizer, cleaned, and saved in .pdb format for further stages [1]. The cleaned proteins were then subjected to docking analysis via the CB-Dock 2 web server [2]. This server automatically identifies the active site of proteins and provides the binding energy of the top 5 conformations between CoGANA and the protein. According to the results, the 5RVW0 protein exhibited the lowest binding energy (BE) with the complex, -7.2 kJ/mol, while 5RVZ and 5RVX proteins showed the highest binding energies, -9.9 and -10.4 kJ/mol, respectively. The CoGANA complex formed two hydrogen bonds with the carboxyl group involving SER A:288 (2.40Å) and LEU A:368 (2.82Å), and two hydrogen bonds with the amino group involving GLN B:664 (2.18Å) and GLN B:594 (2.15Å) in 5RVX. In addition, hydrogen bonding occurred with TYR A:190 (3.17Å) and LEU A:290 (3.09Å) through the nitrogen atom in the ring structure. ASN A:286 (3.28Å), SER A:335 (2.79Å), and ALA A:334 (3.24Å) also formed hydrogen bonds with the carboxyl group of the complex. For 5RVZ, HIS A:223 (3.12Å), LYS A:188 (3.04Å), and TYR A:190 (3.29Å) residues bonded with the oxygen atom of CoGANA’s carboxyl group; THR B:600 (2.17Å) bonded via the hydrogen atom of the carboxyl group; and SER A:288 (1.77Å) bonded through the hydrogen atom of the amino group. Conclusion: For the first time, the molecular docking analysis of the cobalt complex with glutaric acid and nicotinamide (CoGANA) was performed. The results showed that the 5RVZ and 402 Volume 5, Issue 10: Special Issue (EJAR) ISSN: 2181-2020 MPHAPP THE 6TH INTERNATIONAL SCIENTIFIC AND PRACTICAL CONFERENCE “MODERN PHARMACEUTICS: ACTUAL PROBLEMS AND PROSPECTS” TASHKENT, OCTOBER 17, 2025 in-academy.uz 5RVX proteins exhibited the highest binding energies with CoGANA, -9.9 and -10.4 kJ/mol, respectively. This indicates that the binding energy of the ligand molecule (glutaric acid) with these proteins, -5.5 and -5.4 kJ/mol, is 80–93% lower. These results, of course, require further validation through in vivo and in vitro studies.