@article{4c6dca56cb9b44b4b820c43ccca596d5,
title = "Electrostatic Polarization Effect on Cooperative Aggregation of Full Length Human Islet Amyloid",
abstract = "Amyloid aggregation initiates from a slow nucleation process, where the association of monomers is unfavorable in energetics. In principle, the enthalpy change for aggregation should compensate the entropy loss as new monomers attach to formed oligomers. However, the classical force fields with fixed point charges failed to yield the correct enthalpy change due to the lack of electrostatic polarization effect on amyloid aggregation. In this work, we performed molecular dynamics simulation for the full-length human islet amyloid using the polarized protein-specific charges and calculated the electrostatic interaction energy for amyloid oligomers. The results of molecular dynamics simulation show that the aggregates simulated with polarized charges have larger enthalpy change than that with fixed charges. The large enthalpy change mainly originates from the electrostatic polarization, which makes a significant contribution to the cooperative effect of aggregation and facilitates the nucleation process of amyloids.",
author = "Yang Li and Xianwei Wang and Longlong Ren and Xuecheng Cao and Changge Ji and Fei Xia and Zhang, {John Z.H.}",
note = "Funding Information: This work was supported by Natural Science Foundation of Shandong (Grant no. ZR2016BB13), National Natural Science Foundation of China (Grant nos. 11747006, 21433004 and 21703206), National Key R&D Program of China (Grant no. 2016YFA0501700), Natural Science Foundation of Zhejiang (Grant no. LY17B030008). Y.L. also acknowledges the Young Teacher Innovation Fund of Shandong Agricultural University (140-24172) and Key Cultivation Discipline Fund for NSFC of College of Information Science and Engineering. We acknowledge the support of the NYU-ECNU Center for Computational Chemistry at NYU Shanghai. We also thank the Supercomputer Center of East China Normal University for providing us computer time. Funding Information: This work was supported by Natural Science Foundation of Shandong (Grant no. ZR2016BB13), National Natural Science Foundation of China (Grant nos. 11747006, 21433004 and 21703206), National Key R&D Program of China (Grant no. 2016YFA0501700), Natural Science Foundation of Zhejiang (Grant no. LY17B030008). Y.L. also acknowledges the Young Teacher Innovation Fund of Shandong Agricultural University (140-24172) and Key Cultivation Discipline Fund for NSFC of College of Information Science and Engineering.",
year = "2018",
month = aug,
day = "27",
doi = "10.1021/acs.jcim.8b00215",
language = "English (US)",
volume = "58",
pages = "1587--1595",
journal = "Journal of Chemical Information and Modeling",
issn = "1549-9596",
publisher = "American Chemical Society",
number = "8",
}