This article is part of the supplement: Eleventh International Conference on Bioinformatics (InCoB2012): Computational Biology
Blocking Protein kinase C signaling pathway: mechanistic insights into the anti-leishmanial activity of prospective herbal drugs from Withania somnifera
- Equal contributors
1 Department of Biochemical Engineering and Biotechnology, Indian Institute of Technology (IIT) Delhi, Hauz Khas, New Delhi 110016, India
2 Department of Bioinformatics, Alagappa University, Karaikudi, Tamil Nadu 630003, India
3 Department of Biotechnology, Indian Institute of Technology Guwahati, Guwahati 781039, India
BMC Genomics 2012, 13(Suppl 7):S20 doi:10.1186/1471-2164-13-S7-S20Published: 13 December 2012
Leishmaniasis is caused by several species of leishmania protozoan and is one of the major vector-born diseases after malaria and sleeping sickness. Toxicity of available drugs and drug resistance development by protozoa in recent years has made Leishmaniasis cure difficult and challenging. This urges the need to discover new antileishmanial-drug targets and antileishmanial-drug development.
Tertiary structure of leishmanial protein kinase C was predicted and found stable with a RMSD of 5.8Å during MD simulations. Natural compound withaferin A inhibited the predicted protein at its active site with -28.47 kcal/mol binding free energy. Withanone was also found to inhibit LPKC with good binding affinity of -22.57 kcal/mol. Both withaferin A and withanone were found stable within the binding pocket of predicted protein when MD simulations of ligand-bound protein complexes were carried out to examine the consistency of interactions between the two.
Leishmanial protein kinase C (LPKC) has been identified as a potential target to develop drugs against Leishmaniasis. We modelled and refined the tertiary structure of LPKC using computational methods such as homology modelling and molecular dynamics simulations. This structure of LPKC was used to reveal mode of inhibition of two previous experimentally reported natural compounds from Withania somnifera - withaferin A and withanone.