A structural biophysics model of prion protein folding and pathology

Key words: Protein conformational dynamics and folding, prion protein, structural bioinformatics. Prion protein research infographics.

• Lipid membrane composition and GPI anchoring modulate prion protein - membrane surface interactions doi.
  • Fun fact: This article was our first publication that uses a coarse-grained model of a lipid membrane to observe selective prion protein - membrane binding. We compared with the Doppel protein (closest related protein to prion protein) and to our suprise the binding behavior of the two proteins was distinct.
• Templated misfolding: prion protein – fibril recognition.
• Side chain connectivity pattern in the globular domain of the prion protein in mammals explains native conformational dynamics and structural role of pharmacological chaperones that prevent misfolding doi
  • Fun fact: This article was our first publication that demonstrates the usefulness of normal mode analysis combined with network analysis and molecular docking to compare protein structures from the same family across species. A lot of this work happened during the covid pandemic, meeting with students via zoom daily, and each of us doing our best to navigate the unexpected.
• Residue substitutions linked to prion protein misfolding alter the local conformational dynamics of loops doi.
  • Fun fact: This article demonstrates how all-atom MD simulations illustrate conformational preferences in a flexible loop. We learned how to interpret network analysis metrics to make sense of communication across the protein structure