The PLUMED consortium (2019). Promoting transparency and reproducibility in enhanced molecular simulations. Nature Methods, 16(8), 670-673. https://doi.

It has been demonstrated recently that supercooled liquids sharing simple structural features (e.g. pair distribution functions) may exhibit strikingly distinct dynamical behavior. Here we show that a more subtle structural feature correlates with relaxation times in three simulated systems that have nearly identical radial distribution functions but starkly different dynamical behavior. In particular, for the first time we determine the thermodynamic "point-to-set" length scale in several canonical model systems and demonstrate the quantitative connection between this length scale and the growth of relaxation times. Our results provide clues necessary for distinguishing competing theories of the glass transition.

SUMMARY Cells assemble and maintain functionally distinct actin cytoskeleton networks with various actin filament organizations and dynamics through the coordinated action of different sets of actin binding proteins. The biochemical and functional properties of diverse actin binding proteins, both alone and in combination, have been increasingly well studied. Conversely, how different sets of actin binding proteins properly sort to distinct actin filament networks in the first place is not nearly as well understood. Actin binding protein sorting is critical for the self-organization of diverse dynamic actin cytoskeleton networks within a common cytoplasm. Using in vitro reconstitution techniques including biomimetic assays and single molecule multi-color TIRF microscopy, we discovered that sorting of the prominent actin bundling proteins fascin and α-actinin to distinct networks is an intrinsic behavior, free of complicated cellular signaling cascades. When mixed, fascin and α-actinin mutually exclude each other by promoting their own recruitment and inhibiting recruitment of the other, resulting in the formation of distinct fascin- or α-actinin-bundled domains. Subdiffraction-resolution light microscopy and negative staining electron microscopy revealed that fascin domains are densely packed, while α-actinin domains consist of widely spaced parallel actin filaments. Importantly, other actin binding proteins such as fimbrin and espin show high specificity between these two bundle types within the same reaction. Here we directly observe that fascin and α-actinin intrinsically segregate to discrete bundled domains that are specifically recognized by other actin binding proteins.

We investigate the connection between local structure and dynamical heterogeneity in supercooled liquids. Through the study of four different models we show that the correlation between a particle's mobility and the degree of local order in nearby regions is highly system dependent. Our results suggest that the correlation between local structure and dynamics is weak or absent in systems that conform well to the mean-field picture of glassy dynamics and strong in those that deviate from this paradigm. Finally, we investigate the role of order-agnostic point-to-set correlations and reveal that they provide similar information content to local structure measures, at least in the system where local order is most pronounced.Supercooled liquids display markedly heterogeneous dynamics, despite possessing structural properties that appear nearly unchanged from those of normal liquids from which they are prepared [1]. While there has been intense focus on understanding dynamical heterogeneity in a wide variety of systems, the structural origin of this phenomenon is not well understood [2, 3]. Simulations of model supercooled liquids are useful for understanding the connections between structure and dynamics because particle locations may be followed precisely for all times. Nonetheless, new theoretical tools are needed to filter out extraneous detail from the key structural and dynamical fluctuations in glassy systems.One particularly useful simulation-based tool for quantifying the influence of structure on dynamics is the isoconfigurational ensemble, where a large number of molecular dynamics (MD) simulations are initiated from the same starting configuration with momenta sampled randomly from a Boltzmann distribution [4, 5]. Under glassy conditions, spatial heterogeneities are immediately evident in the isoconfigurational displacement (or propensity) field. A reasonable hypothesis is that particles with low propensity have a larger measure of local structural stability. Surprisingly, however, simple structural quantities, such as free volume and local potential energy, show little correlation with the heterogeneity of the propensity field [6]. In some models, localized soft modes [7][8][9] or unstable modes [10] appear to correlate strongly with propensity, but the degree of universality of this connection has not been thoroughly investigated.Recently, focus has turned to the study of specific structural motifs and their putative connection with the dynamics of supercooled liquids. The notion that the frustration of local order incommensurate with bulk crystalline periodicity may be related to glass formation is an old one [11][12][13][14]. New evidence for the growth of domains associated with local packing motifs has been presented for several simple [15] and realistic model systems [16], where particles tend to be found in certain "locally preferred structures" (LPS) with increased supercooling. As a general rule, more fragile systems display a more rapid increase in LPS concentration and domain extent [15, 16]....

The fission yeast actin cytoskeleton is an ideal, simplified system to investigate fundamental mechanisms behind cellular self-organization. By focusing on the stabilizing protein tropomyosin Cdc8, bundling protein fimbrin Fim1, and severing protein coffin Adf1, we examined how their pairwise and collective interactions with actin filaments regulate their activity and segregation to functionally diverse F-actin networks. Utilizing multi-color TIRF microscopy of in vitro reconstituted F-actin networks, we observed and characterized two distinct Cdc8 cables loading and spreading cooperatively on individual actin filaments. Furthermore, Cdc8, Fim1, and Adf1 all compete for association with F-actin by different mechanisms, and their cooperative association with actin filaments affects their ability to compete. Finally, competition between Fim1 and Adf1 for F-actin synergizes their activities, promoting rapid displacement of Cdc8 from a dense F-actin network. Our findings reveal that competitive and cooperative interactions between actin binding proteins help define their associations with different F-actin networks.DOI: http://dx.doi.org/10.7554/eLife.23152.001