Dark Proteome of Newly Emerged SARS-CoV-2 in Comparison with Human and Bat Coronaviruses

Rajanish Giri; Taniya Bhardwaj; Meenakshi Shegane; Bhuvaneshwari R. Gehi; Prateek Kumar; Kundlik Gadhave

The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.03.13.990598 doi: bioRxiv preprint In order to further investigate the nature of the disorder in proteins of SARS-CoV-2, Human SARS, and Bat CoV, we utilized the combined CH-CDF tool that uses the outputs of two binary classifiers of disorder, Charge hydropathy (CH) plot and Cumulative distribution function (CDF) plot. This helped in retrieving more detailed characterization of the global disorder predisposition of the query proteins and their classification according to the disorder "favours". The CH plot is a linear classifier that differentiates between proteins that are predisposed to possess extended disordered conformations that include random coils and premolten globules from proteins that have compact conformations (ordered proteins and molten globule-like proteins). The other binary predictor, CDF is a nonlinear classifier that uses the PONDR ® VLXT scores to discriminate ordered globular proteins from all disordered conformations, which include native molten globules, pre-molten globules, and random coils. The CH-CDF plot can be divided into four quadrants: Q1 (bottom right quadrant) is an area of CH-CDF phase space that is expected to include ordered proteins; Q2 (bottom left quadrant) includes proteins predicted to be disordered by CDF and compact by CH (i.e., native molten globules and hybrid proteins containing high levels of both ordered and disordered regions); Q3 (top left quadrant) contains proteins that are predicted to be disordered by both CH and CDF analysis (i.e., highly disordered proteins with the extended disorder); and Q4 (top right quadrant) possesses proteins disordered according to CH but ordered according to CDF analysis [34] . Figures 2D, 2E and 2F represent the CH-CDF analysis of proteins of SARS-CoV-2, Human SARS, and Bat CoV and show that all the proteins are located within the two quadrants Q1 and Q2. The CH-CDF analysis leads to the conclusion that all proteins of SARS-CoV-2, Human SARS, and Bat CoV are ordered except Nucleocapsid protein, which is predicted to be disordered by CDF but ordered by CH and hence lies in Q2.