Mutant P21 Peptides Could Act As An Improved Cyclin A Inhibitors For Cancer Therapy: An In Silico Validation

Objective: The present study delineates the generation of mutant peptide library from a known anticancer peptide, p21 and in silico evaluation for their affinity towards cyclin. A substrate binding groove. Methods: Mutant peptide library was created based on their AntiCP score and was docked with cyclin A using ClusPro2.0 web server. The docked structures were further simulated into an aqueous environment using Gromacs 4.5.6. Visualization was performed using PyMol software and interaction analysis was done using Discovery Studio Visualizer 4.1 Client and LigPlot plus tool. Results: A total of 57 mutant peptides were generated; out of which only 3 namely, K3C (Lys3Cys), K3F (Lys3Phe), and K3W (Lys3Trp) had a greater affinity for cyclin A than WILD p21 peptide (HSKRRLIFS). Molecular dynamic simulation studies showed that the peptides remained docked into the substrate binding groove throughout the run. Among all the peptides, K3C showed a significantly higher negative binding energy with cyclin A as compared to WILD. Conclusion: The overall results suggested that K3C mutant peptide had ~30 % higher affinity towards cyclin A and thus, could further be explored for its anticancer potential. The study also provides an insight into the crucial interactions governing the recognition of substrate binding groove of cyclin A for the development of novel peptide-based anticancer therapeutics.

Characterization of protease from Alcaligens faecalis and its antibacterial activity on fish pathogens.

Alcaligens faecalis AU01 isolated from seafood industry effluent produced an alkaline protease. The optimum culture conditions for growth as well as enzyme production were 37oC and pH 8. The partially purified protease had specific activity of 9.66 with 17.77% recovery with the molecular weight of 33 kDa and it was active between 30-70oC and optimum being at 55oC and pH 9. The enzyme retains more than 85% activity at 70oC and 78% even at pH 10.The enzyme inhibited the growth of fish pathogens such as Flavobacterium sp., Pseudomonas fluorescens, Vibrio harveyi, Proteus sp. and Vibrio parahaemolyticus. From the present study it can be concluded that Alcaligens faecalis AU01 has the potential for aquaculture as probiotic agent and other several applications.