In-silico Prediction of Drug Target, Molecular Modeling, and Docking Study of Potential Inhibitors against Burkholderia pseudomallei

Abstract

The infection of the Burkholderia pseudomallei causes the disease melioidosis. for which the treatment method takes longer time, and sometimes it is difficult to completely eradicate the bacteria from the body. Moreover, its antibiotic resistance in nature created great concern in recent times. Hence, there is an urgent requirement to identify new drug molecules that can improve the current process of treatments and reduce the risk to people. This study analyzed the pyrimidine metabolic pathways of Burkholderia pseudomallei strain K96243, and UMP (Uridine monophosphate/Uridylate) kinase enzyme was selected as the drug target. After structure prediction by the AlphaFold server, the validation of the structure was performed by using Procheck, Verify3D, and Errat tool. Further, six probable inhibitor molecules were selected from the PubChem database, including the natural inhibitor of the enzyme, Uridine triphosphate (UTP). The molecular docking study predicted that the UTP (CID 6133) had the highest docking score, followed by another compound PubChem (Compound ID) CID 284262. Then, Toxicity and ADMET properties were computed and analyzed. Further, a 5 nanosecond molecular dynamics simulation of the complex of UMP-Kinase and CID 284262 was performed by using the Gromacs 5.1.1 software to analyze the stability of the best complex. It was predicted that the CID 284262 might be considered a suitable inhibitor of the enzyme.