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. 2011 Sep 21;101(6):1432-9.
doi: 10.1016/j.bpj.2011.07.046. Epub 2011 Sep 20.

Relation between molecular shape and the morphology of self-assembling aggregates: a simulation study

Robert Vácha  1 , Daan Frenkel
Affiliations

Relation between molecular shape and the morphology of self-assembling aggregates: a simulation study

Robert Vácha et al. Biophys J. .

Abstract

Proteins can aggregate in a wide variety of structures, both compact and extended. We present simulations of a coarse-grained anisotropic model that reproduce many of the experimentally observed aggregate structures. Conversely, all structures predicted by our model have experimental counterparts (ribbons, multistranded fibrils, and vesicles). The model we use is that of a rodlike particle with an attractive (hydrophobic) stripe on its side. Our Monte Carlo simulations show that aggregate morphologies crucially depend on two parameters. The first one is the width of the attractive stripe and the second one is a presence or absence of attractive interactions at the particle ends. These results provide us with a generic insight into the relation between the shape of protein-protein interaction potential and the morphology of protein aggregates.

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Figures

Figure 1
Figure 1
Schematic representation of a patchy spherocylinder (PSC). The letter L represents the length of the cylindrical part, D denotes its diameter, and u→ is a unit vector along the spherocylinder axis. The vector n→ is a unit vector normal to the spherocylinder axis defining the orientation of the attractive patch.
Figure 2
Figure 2
Graphical representation of the two PSC models. (Blue) The part of the surface that interacts as a hard spherocylinder. (Red) Attractive patches. (Left) PSC-AE (attractive endcaps). (Right) PSC-NE (nonattractive endcaps).
Figure 3
Figure 3
Schematic phase diagram of patchy spherocylinders with L/D = 3, at a volume fraction 4%. The model considered here has attractive endcaps and long-range attraction. The observed phases are: I, isotropic; C, cluster; Fn, fibers (n denotes the number of particles in the cross section of the fiber); B, bilayer. (Black lines) Schematic representation of boundaries between the points with different structures.
Figure 4
Figure 4
Snapshots of observed phases for the PSC-AE model. (Blue) PSCs. (Red spherocylinder) The attractive patch is represented with diameter corresponding to the patch size. The use of periodic boundary conditions allows us to display a cut through the vesicle structures.
Figure 5
Figure 5
Two different structures of four-particle fibers. (Left) Structure corresponds to a wider angular patch. As a consequence, all neighboring particles can interact simultaneously and the patch is oriented toward the geometrical center of the fiber. We denote this structure as “F4”. (Right) Structure corresponds to the case of particles with a narrow attractive stripe. Particles interact strongly with one close neighbor at a time and interact weakly with the particle that is diagonally across from it. We denote this structure as “2F2”.
Figure 6
Figure 6
Schematic phase diagram of the PSC model with nonattractive endcaps (PSC-NE) and long-ranged attraction for L/D = 3 at a volume fraction of 4%. The observed phases are: I, isotropic; C, cluster; CS, crossed stack. (Black lines) Schematic representation of boundaries between the points with different structures.
Figure 7
Figure 7
Snapshots of the aggregate structures of the PSC-NE model. (Blue) PSCs. (Red spherocylinder) The attractive patch is represented with diameter corresponding to the patch size.
Figure 8
Figure 8
Schematic drawing of the intersection of patchy spherocylinder j line segment with the attractive patch of PSC i and its cutoff radius rc. The cut results in an interactive line segment Vj. The expression rij→ is a vector from the geometrical center of interacting line segment Vi to the geometrical center of interacting line segment Vj.
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