Molecular targeting of DNA metabolism by brown algae metabolites in Mycobacterium chelonae: computational analysis via DFT and MD simulations

Mycobacterium chelonae , a member of the rapidly growing mycobacteria, has been linked to a variety of infections, including skin and soft tissue infections, pulmonary disease, and disseminated infections in immunocompromised people. The limited efficacy of current treatments, as well as the emergence of drug resistance, emphasize the need for novel therapeutic interventions. The XTP pyrophosphatase protein is required for M. chelonae survival and proliferation. Its involvement in fundamental cellular processes underscores its potential as a drug target. The Glide tool was employed to dock a library of Phaeophyceae metabolites containing 1200 compounds against the XTP pyrophosphatase protein. Ten highly promising compounds were chosen for further investigation based on their binding affinities. These compounds’ binding affinity ranged from − 7.662 to -6.7 kcal/mol. Only one compound CMNPD27817 showed its expected values to be within an acceptable range after the toxicity risks and ADMET features of the selected compounds were assessed. Docking findings were supported by molecular dynamics simulation. Density functional theory (DFT) analysis further confirmed the electronic stability and favorable charge-transfer properties of CMNPD27817, supporting its potential to form stable interactions with the XTP pyrophosphatase active site. MD simulations indicated that the compound remained associated with the protein binding region over the simulated trajectory. Binding is dW-dominated and the ligand fits well into a hydrophobic binding pocket. This research could lead to the discovery of novel inhibitors of the XTP pyrophosphatase protein, unlocking the development of novel and effective therapeutic agents against M. chelonae .