Abstract Motivation Evolution couples differences in ambient pH to biological function through protonatable groups, in particular, those that switch from buried to exposed and alter protonation state in doing so. We present a tool focusing on structure-based discovery and display of these groups. Results Since prediction of buried group pKas is computationally intensive, solvent accessibility of ionizable groups is displayed, from which the user can iteratively select pKa calculation centers. Results are color-coded, with emphasis on buried groups. Utility is demonstrated with benchmarking against known pH sensing sites in influenza virus hemagglutinin and in variants of murine hepatitis virus, a coronavirus. A pair of histidine residues, which are conserved in coronavirus spike proteins, are predicted to be electrostatically frustrated at acidic pH in both pre- and post-fusion conformations. We suggest that an intermediate expanded conformation at endosomal pH could relax the frustration, allowing histidine protonation and facilitating conformational conversion of coronavirus spike protein. Availability and implementation This tool is available at http://www.protein-sol.manchester.ac.uk/pka/ .
【초록키워드】 coronavirus, motivation, variant, Influenza virus, implementation, coronavirus spike protein, group, Intensive, murine hepatitis virus, conformations, histidine, endosomal pH, residues, solvent, coronavirus spike proteins, ambient, Alter, protonation state, acidic pH, Result, predicted, conserved, demonstrated, conformational, groups, 【제목키워드】 coronavirus, electrostatic,