(Internal) Using AlphaFold to Search for Conserved Motifs in Intrinsically Disordered Proteins

Advisors: Steffen Graether, Molecular and Celular Biology and Sheridan Houghten, Brock University

Proposed Co-advisor: TBC

Intrinsically disordered proteins (IDPs) are proteins that do not have ordered secondary or tertiary structure when alone in solution, breaking the biochemical dogma that the structure of a protein determines its function and vice versa. However, parts of IDPs sometimes do gain structure in the presence of their ligand, a process which is not yet well understood. It is very challenging to identify these regions from sequence alone because the sequence conservation rules are not the same as in well-ordered proteins.  AlphaFold2 is a relatively recently released de novo structure prediction program with surprisingly high accuracy. What is even more surprising is that AlphaFold may have the ability to predict regions of IDPs that fold, and therefore provides a method that does not rely on aligning sequences – in essence these weakly-conserved motifs could be identified through a combination of the conservation of secondary structure prediction and sequence. To validate this approach, the project will compare AlphaFold2 predictions with a database of known IDP ensemble structures, and also with other prediction programs such as ANCHOR.

This is a one-semester project but can be extended to two semesters.