Computational
Identification of DrugBank Compounds targeting Dihydrolipoyl Dehydrogenase: Molecular
Docking and Dynamics Insights
Karlapudi Abraham Peele, Gudavalli Bhavyasri, Kilari Lakshmi Nishitha, Rayidi Chinmai
and Katari Sudheer Kumar
Res. J. Biotech.; Vol. 21(1); 99-107;
doi: https://doi.org/10.25303/211rjbt0990107; (2026)
Abstract
Tuberculosis (TB), driven by Mycobacterium tuberculosis (Mtb), remains a leading
cause of morbidity and mortality worldwide, with the emergence of multidrug-resistant
(MDR) and extensively drug-resistant (XDR) strains posing significant challenges
to existing treatment strategies. This project targets dihydrolipoyl dehydrogenase
(DLD), a critical enzyme involved in Mtb’s central metabolism, virulence and defence
against host-induced oxidative and nitrosative stress. DLD's essential role in cellular
respiration and detoxification highlights it as a promising drug target to combat
resistant TB strains. In this study, molecular docking and molecular dynamics simulations
(MDS) were performed to identify and evaluate potential DLD inhibitors sourced from
the Drug Bank database. Docking analyses revealed DIQUAFOSOL and DARAPLADIB as the
top-performing compounds, with docking scores of -8.7 kcal/mol and -8.5 kcal/mol
respectively. DIQUAFOSOL demonstrated significant interactions, forming eight hydrogen
bonds and DARAPLADIB exhibited two hydrogen bonds. MDS using GROMACS provided insights
into the stability and dynamic behaviour of the ligand-enzyme complexes.
Key parameters, including root mean square deviation (RMSD), root mean square fluctuation
(RMSF), hydrogen bonding, Lennard-Jones (LJ) energies and Coulomb interactions,
were extracted and analysed to assess the binding stability and conformational integrity
of the complexes. The findings underscore the potential of DIQUAFOSOL and DARAPLADIB
as promising DLD inhibitors, paving the way for further experimental validation
and development of novel anti-TB therapies targeting metabolic and detoxification
pathways in Mtb.
