Stabilizing Off-pathway Oligomers by Polyphenol Nanoassemblies for IAPP Aggregation Inhibition
Praveen Nedumpully-Govindan, Aleksandr Kakinen, Emily H Pilkington, Thomas P Davis, Pu Chun Ke, Feng Ding
Scientific Reports | NATURE PUBLISHING GROUP | Published : 2016
Experimental studies have shown that many naturally occurring polyphenols have inhibitory effect on the aggregation of several proteins. Here, we use discrete molecular dynamics (DMD) simulations and high-throughput dynamic light scattering (DLS) experiments to study the anti-aggregation effects of two polyphenols, curcumin and resveratrol, on the aggregation of islet amyloid polypeptide (IAPP or amylin). Our DMD simulations suggest that the aggregation inhibition is caused by stabilization of small molecular weight IAPP off-pathway oligomers by the polyphenols. Our analysis indicates that IAPP-polyphenol hydrogen bonds and π-π stacking combined with hydrophobic interactions are responsible ..View full abstract
Awarded by NIH
Awarded by ARC Project
The work is supported in part by NIH R15ES022766-01A, the startup funds from Clemson University, and ARC Project No. CE140100036. The authors thank Dr. Shane Seabrook for access to the DynaPro Plate Reader. All simulations were performed on the Palmetto high performance cluster, which is managed and maintained by Clemson University CCIT.