Minimal model for self-catalysis in the formation of amyloid-like elongated fibrils

TY - JOUR

T1 - Minimal model for self-catalysis in the formation of amyloid-like elongated fibrils

AU - Di Michele, Lorenzo

AU - Eiser, Erika

AU - Foderà, Vito

PY - 2013/9/19

Y1 - 2013/9/19

N2 - Understanding the mechanism behind protein aggregation is a challenging task that requires a combined use of both experimental and computational approaches. In this work, we present a 2D model for the formation of amyloid-like fibrils. The model allows one to explicitly consider the structural change of the native state of a protein into the aggregation-prone state together with the overall charge of the molecules. By means of Metropolis Monte Carlo and dynamic Monte Carlo, we simulate both the equilibrium and kinetic behavior of an ensemble of model proteins. Our results show the effect of the charge and protein concentration on both the conformational equilibrium and the kinetics of the aggregation process. Specifically, the model is capable of capturing the self-catalytic conversion of native proteins into aggregation-prone ones in the presence of preexisting aggregates, naturally reproducing some peculiar scaling laws observed for a class of amyloidogenic systems.

AB - Understanding the mechanism behind protein aggregation is a challenging task that requires a combined use of both experimental and computational approaches. In this work, we present a 2D model for the formation of amyloid-like fibrils. The model allows one to explicitly consider the structural change of the native state of a protein into the aggregation-prone state together with the overall charge of the molecules. By means of Metropolis Monte Carlo and dynamic Monte Carlo, we simulate both the equilibrium and kinetic behavior of an ensemble of model proteins. Our results show the effect of the charge and protein concentration on both the conformational equilibrium and the kinetics of the aggregation process. Specifically, the model is capable of capturing the self-catalytic conversion of native proteins into aggregation-prone ones in the presence of preexisting aggregates, naturally reproducing some peculiar scaling laws observed for a class of amyloidogenic systems.

U2 - 10.1021/jz401600g

DO - 10.1021/jz401600g

M3 - Journal article

SN - 1948-7185

VL - 4

SP - 3158

EP - 3164

JO - Journal of Physical Chemistry Letters

JF - Journal of Physical Chemistry Letters

ER -