Avoiding Regions Symptomatic of Conformational and Functional Flexibility to Identify Antiviral Targets in Current and Future Coronaviruses

Rahaman, Jordon; Siltberg-Liberles, Jessica

For every protein family, the binary matrices resulting from the different disorder predictions and from the different secondary structure predictions were analyzed in the corresponding evolutionary context using GLOOME. GLOOME (Gain-Loss Mapping Engine) analyzes binary presence and absence patterns in a phylogenetic context . In this study, the Rate4Site option in GLOOME was used to analyze the binary matrices (IUPred 0.4, IUPred 0.5, DISOPRED2, PSIPRED, and JPred) with the corresponding phylogenetic trees to map change of state across sites in each individual protein phylogeny . GLOOME was run with 16 gamma categories and a substitution matrix set to equal rates within each state and transitions between states treated equally. From the binary disorder and order matrices, transition rates between disorder and order or vice versa (DOT) were estimated. From the binary structure and loop matrices, transition rates between structure and loop or vice versa (SLT) were estimated. Similar to Rate4Site, the rates were normalized per protein family with an average across all sites equal to zero and SD equal to 1. This means that sites with a rate <0 are evolving slower than average, while sites with a rate >0 are evolving faster than average.