Research: CANCER Folding Project #12476

Human Pin1 is a peptidyl prolyl isomerase (PPI) involved in many cell signaling processes and a target for cancer therapeutics.

The job of this protein is to recognize proline residues next to phosphorylated serines and threonines, and catalyze the cis/trans isomerization of the proline backbone. Pin1 has two domains that both recognize these motifs: a catalytic domain, and a so-called WW domain, which exists in a conformational equilibrium between and a compact and extended state.

When peptide substrates are present, there is a shift in the conformational equilibrium between compact and extended states, which is in turn coupled to allosteric changes in the catalytic domain that activates the enzyme. The purpose of these simulations is to better learn about the function of Pin1 by modeling the conformational dynamics involved in its allosteric activation.