Bhanu Pratap Gurjar

The biological function of a protein depends on its conformational stability which can be affected by heating, presence of crowders or change in pH. The study investigates the aggregation behaviour of α-Lactalbumin (α-LA) in presence of crowders like polyethylene glycol and its monomer ethylene glycol at different pH values. The findings provide a comprehensive understanding of protein’s adaptability towards conformational changes under variable physicochemical conditions by using multiple spectroscopic, fluorescence and computational methods. The results show that α-LA exhibits pH dependent conformational transition from native state to partially unfolded state and finally to aggregation prone state as the pH changes. Ethylene glycol (EG) and PEG400 show a dual effect, aggregation inhibition under acidic conditions (pH 2.0-4.5) and aggregation promotion effect under neutral to basic conditions (pH 7.0, 9.0, and 12.0). The decrease in pH gradually decreases the unfolded state of α-LA to decrease the β-sheet content and thus increase the α-LA stability in the solution. While an increase in pH promotes α-LA aggregate formation, thereby decreasing the α-LA stability. The observed dual effect may indicate that both crowders not only modify the solvent properties but also influence the energy landscape that governs the folding pathways. Overall, this work highlights the mechanistic basis of crowder-mediated modulation of α-LA sensitivity towards pH changes, providing its relevance to physiological behaviour, formulation stability, and biotechnological handling.

Tuberculosis (TB) remains a major global health challenge, necessitating the development of novel therapeutic interventions. Enoyl-acyl carrier protein (ACP) reductase (InhA), a key enzyme in the fatty acid biosynthesis pathway of Mycobacterium tuberculosis, has emerged as a promising target for anti-TB drug discovery. Exploration of InhA-inhibitors is important for advancing the drug discovery process. This study systematically investigates the molecular and pharmacological interactions of bioactive phytochemicals from Indian traditional medicinal plants with InhA to elucidate their therapeutic potential. Among 42 screened phytocompounds, the top five (Ebastine, 2-Phenylaminoadenosine, Gosogliptin, Lorcainide, and Levomefolic acid) showed promising binding affinities towards InhA (PDB: 2X22), with binding free energy ranging from −9.6 to −10.9 kcal/mol. Comprehensive computational analyses, including pharmacokinetic predictions, drug-likeness evaluation, and biological activity assessment, highlighted their potential as a drug candidate. These top-ranking ligands exhibited potential target-lead interactions, forming stable hydrogen bonds and hydrophobic contacts crucial for inhibitory activity. This multidisciplinary computational approach, including molecular docking and dynamic simulations, identifies these phytochemicals as high-affinity and stable inhibitors of InhA. These identified phytocompounds could serve as promising scaffolds for further optimization and experimental validation in the quest for new plant-based anti-TB agents.