Journal of Computer Science & Systems Biology

Gayathri Ramasubban

Publications

• Research Article
  In silico Analysis of Novel Mutation ala102pro Targeting pncA Gene of M. Tuberculosis
  Author(s): Dhanurekha Lakshmipathy, Gayathri Ramasubban, Lily Therese, Umashankar Vetrivel, Muthukumaran Sivashanmugam, Sunitha Rajendiran, Sridhar R, Madhavan HN and Meenakshi NDhanurekha Lakshmipathy, Gayathri Ramasubban, Lily Therese, Umashankar Vetrivel, Muthukumaran Sivashanmugam, Sunitha Rajendiran, Sridhar R, Madhavan HN and Meenakshi N
  
  This study reports on the structural and functional basis of pyrazinamide (PZA) resistance conferred by a novel mutation Ala102Pro in pncA gene as sequenced from a PZA resistant Mycobacterium tuberculosis strain. Molecular modeling studies of Wild Type (WT) and Mutant Type (MT) of Pyrazinamidase (PZase) showed the mutation at Ala102Pro does not impact on the conformation of the protein. However, the docking studies infer that MT has a higher inhibitory constant (Ki-990.0m) compared to WT (Ki-822.42m), which is indicative of drug resistance in MT. Furthermore, molecular interaction studies also reveal that WT forms 4 hydrogen bonds involved in PZA-WT Inhibitory interactions, whereas, in case of MT, it formed 5 hydrogen bonds with PZA. However, Ala102 in WT was found to be less fluctuating and more stable in Molecular dynamics Simulation when compared to Pro.. Read More»
  DOI: 10.4172/jcsb.1000103

  Abstract PDF