The mce1 operon of Mycobacterium tuberculosis, which codes the Mce1 transporter, facilitates the transport of fatty acids. Fatty acids are one of the major sources for carbon and energy for the pathogen during its intracellular survival and pathogenicity. The mce1 operon is transcriptionally regulated by Mce1R, a VanR-type regulator, which could bind specific ligands and control the expression of the mce1 operon accordingly. This work reports computational identification of Mce1R-specific ligands. Initially by employing cavity similarity search algorithm by the ProBis server, the cavities of the proteins similar to that of Mce1R and the bound ligands were identified from which fatty acids were selected as the potential ligands. From the earlier-generated monomeric structure, the dimeric structure of Mce1R was then modeled by the GalaxyHomomer server and validated computationally to use in molecular docking and molecular dynamics simulation analysis. The fatty acid ligands were found to dock within the cavity of Mce1R and the docked complexes were subjected to molecular dynamics simulation to explore their stabilities and other dynamic properties. The data suggest that Mce1R preferably binds to long-chain fatty acids and undergoes distinct structural changes upon binding.
Keywords: MD simulation; Mce1R; Molecular docking; Protein–ligand interaction; Rv0165c; VanR family.
© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.