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.

Microbial production of L-tyrosine: a review.

Microbial production of L-tyrosine by direct fermentation and by enzymatic methods has been reviewed. Achievements in this regard made through recombinant DNA techniques have also been included. The review also includes biosynthesis and regulation of tyrosine.

Microbial production of L-tryptophan: a review.

Microbial production of L-tryptophan has been reviewed with 172 references. The review includes different tryptophan producing microorganisms, their optimal cultural conditions, yields, assay and process of recovery. It also includes a discussion on the pathway of tryptophan biosynthesis and its regulation. Achievements in this regard made through genetic engineering have also been included.

Microbial production of L-phenylalanine: a review.

Microbial production of L-phenylalanine by direct fermentation and by substrate conversion has been reviewed. The review also includes a discussion on different other methods for phenylalanine production, their advantages and disadvantages with mutants and genetically tailored strains. Biosynthesis of phenylalanine, its regulation in hyperproducing strains and recovery of phenylalanine has been discussed in brief.