Marine sponges have potential sources for secondary metabolites and are considered as a drug treasure house. In this work, 3D model of Mycothiol-S-conjugate amidase (Mca) was determined by comparative homology modeling program MODELLER based on the crystal structure of 1-D-myo-inositol 2-acetamido-2-deoxy-alpha-D-glucopyranoside deacetylase (MshB) from Mycobacterium tuberculosis as a template. The computed model's energy was minimized and validated to obtain a stable model structure. Stable model was used for docking of nineteen bioactive compounds isolated from marine sponges against Mca using AutoDock 4.2. The docked complexes were validated and enumerated based on the AutoDock Scoring function to pick out the best marine inhibitors based on binding energy. Thus from the entire marine compounds which were docked, we got best one (Arenosclerin E) of them with optimal binding energy -13.11 kcal/mol. Further the best-docked complex was analyzed through Python Molecular Viewer software for their interaction studies. The docked protein - inhibitor complex structure was optimized using molecular dynamics simulation for 5 ps with the CHARMM-22 force field using NAMD incorporated in VMD 1.9.2 and then evaluating the stability of complex structure by calculating RMSD values. Thus from the Complex scoring and binding ability its deciphered that this marine derived compound could be promising inhibitor for Mca as drug target yet pharmacological studies have to confirm it.
Keywords: Mca; Mycobacterium tuberculosis; Mycothiol-S-conjugate amidase; NAMD; VMD.