Molecular Insights into the Conformational and Binding Behaviors of Human Serum Albumin Induced by Surface-Active Ionic Liquids.

Extensive research has been carried out to investigate the stability and function of human serum albumin (HSA) when exposed to surface-active ionic liquids (SAILs) with different head groups (imidazolium, morpholinium, and pyridinium) and alkyl chain lengths (ranging from decyl to tetradecyl). Analysis of the protein fluorescence spectra indicates noticeable changes in the secondary structure of HSA with varying concentrations of all SAILs tested. Helicity calculations based on the Fourier transform infrared (FTIR) data show that HSA becomes more organized at the micellar concentration of SAILs, leading to an increased protein activity at this level. Small-angle neutron scattering (SANS) data confirm the formation of a bead-necklace structure between the SAILs and HSA. Atomistic molecular dynamics (MD) simulation results identify several hotspots on the protein surface for interaction with SAIL, which results in the modulation of protein conformational fluctuation and stability. Furthermore, fluorescence resonance energy transfer (FRET) experiments with the intramolecular charge transfer (ICT) probe trans-ethyl p-(dimethylamino) cinnamate (EDAC) demonstrate that higher alkyl chain lengths and SAIL concentrations result in a significantly increased energy transfer efficiency. The findings of this study provide a detailed molecular-level understanding of how the protein structure and function are affected by the presence of SAILs, with potential implications for a wide range of applications involving protein-SAIL composite systems.

A multidrug efflux protein in Mycobacterium tuberculosis; tap as a potential drug target for drug repurposing.

Tuberculosis (TB) is a serious communicative disease caused by Mycobacterium tuberculosis. Although there are vaccines and drugs available to treat the disease, they are not efficient, moreover, multidrug-resistant TB (MDR-TB) become a major hurdle in its therapy. These MDR strains utilize the multidrug efflux pump as a decisive weapon to fight against antitubercular drugs. Tap membrane protein was observed as a crucial multidrug efflux pump in M. tuberculosis and its critical implication in MDR-MTB development makes it an effective drug target. In the present study, we have utilized various in silico approaches to predict the applicability of FDA-approved ion channel inhibitors and blockers as therapeutic leads against Tuberculosis by targeting multidrug efflux protein; Tap in MTB. Tap protein structure is predicted by Phyre2 server followed by model refinement, validation, physio-chemical catheterization and target prediction. Further, the interaction between Tap protein and ligands were analysed by molecular docking and MD simulation run of 100 ns. Based on implication and compatibility, 18 FDA-approved ion channel inhibitors and blockers are selected as a ligand against the Tap protein and eventually observed five ligands; Glimepiride, Flecainide, Flupiritine, Nimodipine and Amlodipine as promising compounds which have exhibited the significant stable interaction with Tap protein and are proposed to modulate or interfere with its activity. These compounds illustrated the substantial docking score and total binding enthalpy more than -7 kcal/mol and -42 kcal/mol respectively which implies that the selected FDA-approved compounds can spontaneously interact with the Tap protein to modulate its function. This study proposed Tap protein as a prominent drug target in MTB and investigated compounds that show considerable interaction with the Tap protein as potential therapeutic molecules. These interactions may lead to modulating or inhibit the activity of drug efflux protein thereby making MTB susceptible to antitubercular drugs.