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

Advisor: Steffen Graether, Molecular and Cellular Biology

Proposed computational advisor: Sheridan Houghton (Brock)

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 since the sequence conservation rules are not the same as for ordered proteins.  AlphaFold is a 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 project is suitable for one or two semesters. The student is required to occasionally be on-site.

Knowledge/Skills

Protein sequences, protein structure, structure prediction is an asset but not required