12. Interpret biological phenomena
With the generated model various biological and medicine-related aspects
could be explained. Based on type of model, various aspects related to
the structure, protein function, regulation, modification, activation
etc. can be predicted. In addition to several CASP challenges also
Critical Assessment of protein Function Annotation (CAFA,
https://www.biofunctionprediction.org/cafa/) challenges have addressed
and boosted development of methods for biological interpretation. As an
example, a study describes in addition to the quality of model,
relevance and accuracy of numerous biological and medical predictions
made based on 15 blind prediction models (Khan and Vihinen, 2009).
Example: The conserved R520 is located at the N terminus of the
catalytic loop where it is structurally and functionally vital. In cAPK,
the corresponding R165 interacts with the stable T197 phosphorylation
site. Both of these residues are conserved also in BTK; however, the
corresponding phosphorylated residue is tyrosine in PTKs, Y551 in BTK.
This residue precedes the homologue for T197 in cAPK. Many kinases are
activated by phosphorylation at either of these sites. According to the
BTK model, the phosphorylated Y551 could interact with R520. Variation
R520E causes XLA without detectable B lymphocytes, presumably because of
the lack of contact between the catalytic loop and the regulatory
phosphorylation site.