Multiscale Models for Fibril Formation: Rare Events Methods, Microkinetic Models, and Population Balances.

ABSTRACT: Amyloid fibrils are thought to grow by a two-step dock-lock mechanism. However, previous simulations of fibril formation (i) overlook the bi-molecular nature of the docking step and obtain rates with first-order units, or (ii) superimpose the docked and locked states when computing the potential of mean force for association and thereby muddle the docking and locking steps. Here, we developed a simple microkinetic model with separate locking and docking steps and with the appropriate concentration dependences for each step. We constructed a simple model comprised of chiral dumbbells that retains qualitative aspects of fibril formation. We used rare events methods to predict separate docking and locking rate constants for the model. The rate constants were embedded in the microkinetic model

SUBMITTER: Shayesteh Zadeh A 

PROVIDER: S-EPMC8234428 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature