COMPUTATIONAL STUDY ON BINDING AFFINITY OF RPOB MUTANTS WITHPHYTOCHEMICALS

Objective: The aim of the study was to study the binding affinity of RpoB and its mutants with the phytochemicals computationally to find out the potential drug against Tuberculosis. Methods: The mutants of RpoB protein were modelled using MODELLER9v10 and the docking analysis were performed using iGEMDOCKv2.1 program and the docking results of mutants and wild type rpoB were compared. Some phytochemicals were explored and their interaction with mutants and wild type was taken into consideration. Results: Mycobacterium tuberculosis bacterium has form resistance to conventional drugs such as rifampicin, isoniazid, betaquiline etc. Due to mutation in rpoB region Mycobacterium tuberculosis has become resistant to rifampicin. Generally, mutations are caused at 81 base pair of RRDR (RIF Resistance determining region) of the rpoB gene. Mutations at 531(S531L), 513(Q513K), 533(L533P), 516(D516V), 526(H526C) are mainly associated with RIF resistance. On comparison of results, it was determined that mutants show lesser affinity with Rifampicin in comparison to wild type rpoB. This showed that the mutants show resistance against Rifampicin. Selected phytochemicals show lesser energies with the wild as well as mutants and hence, can be selected as a possible treatment to the disease. Conclusion: Due to Mutations bacterium have become resistance to the drugs such as rifampicin and isoniazid etc. and hence they are ineffective in the disease. There is an emergent need for de novo drugs which can be used as a possible treatment for this disease and phytochemicals can be used as possible future drug candidate.