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). 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. 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. 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. 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. These results were
published at Qin, Bowman, and Huang, 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. 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! We also welcome more clients to try out the new NaCl
Folding@home core. If you are interested in this new core, you can
download it from the Chrome Store
(https://chrome.google.com/webstore/detail/foldinghome/hmnbjdgjgikbkapaolimfoidihobnofo).