In the past couple of years, Xuhui Huang’s group at HKUST
(http://compbio.ust.hk/) has performed large-scale molecular dynamics
simulations at Folding@Home (Project 2974-2975) to investigate the
mis-folding of the hIAPP (human islet amyloid polypeptide, also called
amylin).
Like other misfolding peptides, hIAPP is generally unstructured in
water solution but adopts an alpha-helix structure when binds to the
cellular membrane. Around 95% of patients with Type II diabetes
exhibit large deposits of misfolded hIAPP (beta-sheet fibrils). Â The
aggregation of this peptide is suggested to induce apoptotic
cell-death in insulin-producing β-cells that may further cause the
development of the type II diabetes. Â Using Markov state models
constructed from many molecular dynamics simulations, we have
identified the metastable conformational states of the hIAPP monomer
and the dynamics of transitioning between them. Â We show that even
though the overall structure of the hIAPP peptide lacks a dominant
folded structure, there exist a large number of reasonably populated
metastable conformational states. Â Among them, a few states containing
substantial amounts of β-hairpin secondary structure and extended
hydrophobic surfaces may further induce the nucleation of hIAPP
aggregation and eventually form the fibrils. Â These results were
published at Qin, Bowman, and Huang, Â J. Am. Chem. Soc., 135 (43),
16092–16101, (2013) (http://pubs.acs.org/doi/full/10.1021/ja403147m).
In 2014, our lab in collaboration with the Pande group at Stanford
University has successfully developed a new Folding@home client that
can run at the Chrome Web Browsers. Â This new core is implemented on
Google Chrome’s Native Client (NaCl) platform (details here:
https://foldingathome.org/adding-a-completely-new-way-to-fold-directly-in-the-browser/).
Currently we have set up a NaCl folding server at Hong Kong
(folding5.ust.hk) to continue our study on the aggregation of the
hIAPP peptides.  Up to now, folding5.ust.hk has collected a few TBs
molecular dynamics simulation data of the hIAPP peptides.
We would like to thank all the donors for their generous
contributions! Â We also welcome more clients to try out the new NaCl
Folding@home core. Â If you are interested in this new core, you can
download it from the Chrome Store
(https://chrome.google.com/webstore/detail/foldinghome/hmnbjdgjgikbkapaolimfoidihobnofo).