@article{10.1371/journal.pcbi.1000357, doi = {10.1371/journal.pcbi.1000357}, author = {Jiang, Ping AND Xu, Weixin AND Mu, Yuguang}, journal = {PLOS Computational Biology}, publisher = {Public Library of Science}, title = {Amyloidogenesis Abolished by Proline Substitutions but Enhanced by Lipid Binding}, year = {2009}, month = {04}, volume = {5}, url = {https://doi.org/10.1371/journal.pcbi.1000357}, pages = {1-13}, abstract = {The influence of lipid molecules on the aggregation of a highly amyloidogenic segment of human islet amyloid polypeptide, hIAPP20–29, and the corresponding sequence from rat has been studied by all-atom replica exchange molecular dynamics (REMD) simulations with explicit solvent model. hIAPP20–29 fragments aggregate into partially ordered β-sheet oligomers and then undergo large conformational reorganization and convert into parallel/antiparallel β-sheet oligomers in mixed in-register and out-of-register patterns. The hydrophobic interaction between lipid tails and residues at positions 23–25 is found to stabilize the ordered β-sheet structure, indicating a catalysis role of lipid molecules in hIAPP20–29 self-assembly. The rat IAPP variants with three proline residues maintain unstructured micelle-like oligomers, which is consistent with non-amyloidogenic behavior observed in experimental studies. Our study provides the atomic resolution descriptions of the catalytic function of lipid molecules on the aggregation of IAPP peptides.}, number = {4}, }