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

Rahaman, Jordon; Siltberg-Liberles, Jessica

The accuracy of PSIPRED and JPred's secondary structure predictions are about 80% (Bryson et al. 2005; Drozdetskiy et al. 2015) . PSIPRED has been found to rarely predict an alpha helix instead of a beta strand and vice versa, and most of the PSIPRED errors are due to secondary structure not being predicted (Li et al. 2014) . When secondary structure is not conserved for the same site in a multiple sequence alignment, it suggests that the secondary structure prediction may be 1) inaccurate, 2) not predicted with high confidence, or 3) the regions are indeed metamorphic; they can transition from one element to another. Although (1) is difficult to address without experimentally determined structures for all sequences, (2) and (3) are not necessarily incompatible interpretations because low confidence secondary structure prediction could indicate metamorphic secondary structure regions. Metamorphic secondary structure regions have interesting consequences for conformational and functional flexibility.