Understanding the folding of hIAPP, the peptide linked to the Type 2 diabetes

Here's an update from Prof. Xuhui Huang's lab at Hong Kong University of Science and Technology, another collaborating labortory in the Folding@home consortium.

XuhuiHuang_picIn addition to the molecular recognition processes, another project his lab is working on at the Folding@home platform is to explore the folding free energy landscape of the human islet amyloid polypeptide (hIAPP).  hIAPP (also called amylin) is a 37-residue peptide and its aggregation reduces working β-cells in patients with Type 2 diabetes.  As an intrinsically disordered protein, hIAPP monomer does not have a folded global minimum in its folding free energy landscape, but contains many stable local minimums.  Thus understanding the nature of these locally metastable states can help us to understand the mechanisms of the hIAPP aggregation, and further design small molecules to inhibit the amyloid formation.  

Just as we have seen in the Pande lab simulations of the Aß peptide in Alzheimer's run on Folding@home previously, this research may offer potential therapeutic agents for Type 2 diabetes.  At Folding@home, we are currently running extensive molecular dynamics (MD) simulations and construct Markov State Model to elucidate the free energy landscape of the hIAPP monomer.  Projects 2974 and 2975 are related to the above project. We would like to thank all the Folding@home donors for your help to make our research possible.