Mechanisms and Kinetics of Amyloid Aggregation Investigated by a Phenomenological Coarse-Grained Model - Computational Modeling of Biological Systems - page 192

To overcome such computational limitations, simplified models have been
developed and used to investigate the kinetics and pathways of oligomerization and
fibril formation at different levels of resolution [ 36 ]. In this chapter, we first review
briefly the simplified models of aggregation. We then present our coarse-grained
phenomenological (CGF) model of an amphipathic peptide [ 37 ], and its use for
studying kinetics and thermodynamics, both in bulk conditions and in presence of
other simplified (macro)molecules.

2 Coarse-Grained Models

In coarse-grained models, the complexity of a system (and therefore the compu-
tational cost) is reduced by grouping atoms into larger units or “beads,” whose
mutual interactions are usually approximated by a potential of mean force [ 38 ].
Several coarse-grained models of different resolutions have been developed to
study aggregation (see Fig. 1 ). Zhang and Muthukumar [ 39 ] have created a cuboid
model able of reproducing the features of a nucleation-limited aggregation process.
With their so-called “tube” model, Auer and coworkers [ 40 ] have shed light upon
the conversion of a disordered aggregate into an aggregating nucleus. Higher-
resolution models like the one developed by Thirumalai and collaborators [ 41 ]

Fig. 1 Main coarse-grained models discussed in Sect. 2. ( a ) Cuboid model [ 39 ]; ( b ) tube model
[ 40 ]; ( c ) lattice model [ 41 ]; ( d ) CGF model [ 37 ]; ( e ) Shea model [ 43 ]; ( f ) Hall model [ 42 ].
Reprinted from [ 36 ] with permission by Elsevier