Thermodynamic Stability of Polar and Nonpolar Amyloid Fibrils

Farbod Mahmoudinobar; Jennifer M. Urban; Zhaoqian Su; Bradley L. Nilsson; Cristiano L. Dias

doi:10.1021/acs.jctc.9b00145

Thermodynamic Stability of Polar and Nonpolar Amyloid Fibrils

Farbod Mahmoudinobar, Jennifer M. Urban, Zhaoqian Su, Bradley L. Nilsson, Cristiano L. Dias

Physics

Research output: Contribution to journal › Article › peer-review

17 Scopus citations

Abstract

Thermodynamic stabilities of amyloid fibrils remain mostly unknown due to experimental challenges. Here, we combine enhanced sampling methods to simulate all-atom models in explicit water in order to study the stability of nonpolar (Aβ_16-21) and polar (IAPP_28-33) fibrils. We find that the nonpolar fibril becomes more stable with increasing temperature, and its stability is dominated by entropy. In contrast, the polar fibril becomes less stable with increasing temperature, while it is stabilized by enthalpy. Our results show that the nature of side chains in the dry core of amyloid fibrils plays a dominant role in accounting for their thermodynamic stability.

Original language	English (US)
Pages (from-to)	3868-3874
Number of pages	7
Journal	Journal of Chemical Theory and Computation
Volume	15
Issue number	6
DOIs	https://doi.org/10.1021/acs.jctc.9b00145
State	Published - Jun 11 2019

All Science Journal Classification (ASJC) codes

Computer Science Applications
Physical and Theoretical Chemistry

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abstract = "Thermodynamic stabilities of amyloid fibrils remain mostly unknown due to experimental challenges. Here, we combine enhanced sampling methods to simulate all-atom models in explicit water in order to study the stability of nonpolar (Aβ16-21) and polar (IAPP28-33) fibrils. We find that the nonpolar fibril becomes more stable with increasing temperature, and its stability is dominated by entropy. In contrast, the polar fibril becomes less stable with increasing temperature, while it is stabilized by enthalpy. Our results show that the nature of side chains in the dry core of amyloid fibrils plays a dominant role in accounting for their thermodynamic stability.",

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AU - Mahmoudinobar, Farbod

AU - Urban, Jennifer M.

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AU - Nilsson, Bradley L.

AU - Dias, Cristiano L.

PY - 2019/6/11

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AB - Thermodynamic stabilities of amyloid fibrils remain mostly unknown due to experimental challenges. Here, we combine enhanced sampling methods to simulate all-atom models in explicit water in order to study the stability of nonpolar (Aβ16-21) and polar (IAPP28-33) fibrils. We find that the nonpolar fibril becomes more stable with increasing temperature, and its stability is dominated by entropy. In contrast, the polar fibril becomes less stable with increasing temperature, while it is stabilized by enthalpy. Our results show that the nature of side chains in the dry core of amyloid fibrils plays a dominant role in accounting for their thermodynamic stability.

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Thermodynamic Stability of Polar and Nonpolar Amyloid Fibrils

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