TY - JOUR
T1 - Thermodynamic Stability of Polar and Nonpolar Amyloid Fibrils
AU - Mahmoudinobar, Farbod
AU - Urban, Jennifer M.
AU - Su, Zhaoqian
AU - Nilsson, Bradley L.
AU - Dias, Cristiano
PY - 2019/6/11
Y1 - 2019/6/11
N2 - 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.
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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U2 - 10.1021/acs.jctc.9b00145
DO - 10.1021/acs.jctc.9b00145
M3 - Article
C2 - 31038946
AN - SCOPUS:85066888976
SN - 1549-9618
VL - 15
SP - 3868
EP - 3874
JO - Journal of Chemical Theory and Computation
JF - Journal of Chemical Theory and Computation
IS - 6
ER -