In silico study of cox protein from P2 type enteric bacteriophages based on sequence, structure and dynamics to understand its functional integrity

Abstract

Cox protein plays a critical role in deciding the lytic-lysogenic switch of P2 enteric phages. This phenomenon makes Cox protein one of the most important candidates in developing novel phage-based therapeutics against antibacterial resistant pathogens. The principle focus concerning protein and its decision making is a DNA binding event, which helps to regulate differential promoter expression. In the current study, we have attempted to understand the sequence, structural and dynamic features associated with Cox protein and its DNA binding. Unavailability of information was a big burden in further proceedings. We have done an extensive literature search to develop a database of Cox with relevant information. That information coupled with the methods of Sequence-based phylogenetic and conservation studies, Homology Modelling, Atomic-level Docking and Molecular Dynamics (MD) Simulation (50 ns each for 10 systems, i.e. total of 500 ns) were performed in the current study. Analysis of those extensive studies has provided us the required sequence to structure to dynamics to functional understanding. Our present study would indeed be very helpful in understanding the biochemical mechanism of Cox activation as well as designing potential phage therapeutics.

Graphical Abstract

Keywords:

• Cox protein
• DNA binding protein
• enterobacteriophage
• homology modelling
• molecular dynamics simulation
• Gromacs
• free energy landscape
• principal component analysis
• normal mode analysis

Acknowledgements

The authors are thankful to the Head, Department of Botany and Microbiology, Gurukula Kangri (Deemed to be University) for providing computer facility. We wish to thank to the other institutions for helping for conducting a part of the work, namely ICC (IIT-Roorkee), Bioinformatics Facility, Department of Biosciences and Bioengineering (IIT-Roorkee), and Bioinformatics Resources and Applications Facility (BRAF), C-DAC (Pune) for the provision of computational facilities and support.

Disclosure statement

No potential conflict of interest was reported by the authors.

Funding

The author(s) reported there is no funding associated with the work featured in this article.