Role of nitrogen containing heterocyclic compounds in acyl Co-A carboxylase carboxyltransferase: Docking with dynamic simulation studies

Abstract

Acyl Co-A carboxylase carboxyltransferase (AccD5) is essential for cell wall lipid biosynthesis and its disruption leads to mycobacterial death. Acyl CoA is the key regulation point for fatty acid synthesis and therefore AccD5 has become a good target for mycobacterial disease. Herein, docking and Molecular dynamic simulations with other computational techniques and softwares has been used to select the best compound. The heterocyclic compounds were indole, n-methylpiperazine, piperidine, and pyrrolidine derivatives. Among which, the docking results showed Ib5, an indole containing heterocyclic compound, as a potent inhibitor with good binding affinity with -20.23 kcal/mol of energy as compared with the standard NCI-65828 (8-amino-5-(4’-hydroxybiphenyl-4ylazo)naphthalene-2-sulfonate molecule with -19.24 kcal/mol of binding energy. Additionally, MD simulations showed less fluctuations with depiction of root means square deviation and root mean square fluctuation graphs in 2A7S-Ib5 complex. Wherein, this molecular modeling of AccD5 with Ib5 provided an insight to use it as an anti-tubercular drug. Therefore, this method has helped to prove the nitrogen containing heterocyclic compounds can be used against Mycobacterium tuberculosis.