02306nas a2200301   4500000000100000008004100001260001200042653001200054653001900066653002500085653002200110653003400132653002200166100001100188700001500199700001400214700001000228700001100238700001200249700001300261700001200274700001300286700001200299245011000311300000900421520156000430022001401990       2023                            d  c01/202310aleprosy10aDrug Discovery10ainteraction analysis10aMolecular Docking10amolecular dynamics simulation10anatural compounds1 aKhan S1 aPunnoose K1 aBishara N1 aAli R1 aKhan S1 aAhmad S1 aMarouf H1 aMirza S1 aIshrat R1 aHaque S00aIdentification of potential inhibitor molecule against MabA protein of  by integrated in silico approach.  a1-163 a<p>Leprosy is one of the chronic diseases with which humanity has struggled globally for millennia. The potent anti-leprosy medications rifampicin, clofazimine and dapsone, among others, are used to treat leprosy. Nevertheless, even in regions of the world where these drugs have been successfully implemented, resistance continues to be observed. Due to the problems with the current treatments, this disease should be fought at every level of society with new drugs. The purpose of this research was to identify natural candidates with the ability to inhibit MabA (gene-fabG1) with fewer negative effects. The work was accomplished through molecular docking, followed by a dynamic investigation of protein-ligand, which play a significant role in the design of pharmaceuticals. After modelling the protein structure with MODELLER 9.21v, AutoDock Vina was used to perform molecular docking with 13 3 D anti-leprosy medicines and a zinc library to determine the optimal protein-ligand interaction. In addition, the docking result was filtered based on binding energy, ADMET characteristics, PASS analysis and the most crucial binding residues. The ZINC08101051 chemical compound was prioritized for further study. Using an all-atom 100 ns MD simulation, the binding pattern and conformational changes in protein upon ligand binding were studied. Recommendation for subsequent validation based on deviation, fluctuation, gyration and hydrogen bond analysis, followed by main component and free energy landscape.Communicated by Ramaswamy H. Sarma.</p>
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