Phase Diagram of alpha-Helical and beta-Sheet Forming Peptides

The intrinsic property of proteins to form structural motifs such as alpha-helices and beta-sheets leads to a complex phase behavior in which proteins can assemble into various types of aggregates including crystals, liquidlike phases of unfolded or natively folded proteins, and amyloid fibrils. Here we use a coarse-grained protein model that enables us to perform Monte Carlo simulations for determining the phase diagram of natively folded alpha-helical and unfolded beta-sheet forming peptides. The simulations reveal the existence of various metastable peptide phases. The liquidlike phases are metastable with respect to the fibrillar phases, and there is a hierarchy of metastability

Nucleation of colloids and macromolecules: does the nucleation pathway matter?

A recent description of diffusion-limited nucleation based on fluctuating hydrodynamics that extends classical nucleation theory predicts a very non-classical two-step scenario whereby nucleation is most likely to occur in spatially-extended, low-amplitude density fluctuations. In this paper, it is shown how the formalism can be used to determine the maximum probability of observing \emph{any} proposed nucleation pathway, thus allowing one to address the question as to their relative likelihood, including of the newly proposed pathway compared to classical scenarios. Calculations are presented for the nucleation of high-concentration bubbles in a low-concentration solution of globular proteins and it is found that the relative probabilities (new theory compared to classical result) for reaching a critical nucleus containing $N_c$ molecules scales as $e^{-N_c/3}$ thus indicating that for all but the smallest nuclei, the classical scenario is extremely unlikely.Comment: 7 pages, 5 figure

Stochastic self-assembly of incommensurate clusters

We examine the classic problem of homogeneous nucleation and growth by deriving and analyzing a fully discrete stochastic master equation. Upon comparison with results obtained from the corresponding mean-field Becker-D\"{o}ring equations we find striking differences between the two corresponding equilibrium mean cluster concentrations. These discrepancies depend primarily on the divisibility of the total available mass by the maximum allowed cluster size, and the remainder. When such mass incommensurability arises, a single remainder particle can "emulsify" or "disperse" the system by significantly broadening the mean cluster size distribution. This finite-sized broadening effect is periodic in the total mass of the system and can arise even when the system size is asymptotically large, provided the ratio of the total mass to the maximum cluster size is finite. For such finite ratios we show that homogeneous nucleation in the limit of large, closed systems is not accurately described by classical mean-field mass-action approaches.Comment: 5 pages, 4 figures, 1 tabl

Heterogeneous condensation of the Lennard-Jones vapor onto a nanoscale seed particle

The heterogeneous condensation of a Lennard-Jones vapor onto a nanoscale seed particle is studied using molecular dynamics simulations. Measuring the nucleation rate and the height of the free energy barrier using the mean first passage time method shows that the presence of a weakly interacting seed has little effect on the work of forming very small cluster embryos but accelerates the rate by lowering the barrier for larger clusters. We suggest that this results from a competition between the energetic and entropic features of cluster formation in the bulk and at the heterogeneity. As the interaction is increased, the free energy of formation is reduced for all cluster sizes. We also develop a simple phenomenological model of film formation on a small seed that captures the general features of the nucleation process for small heterogeneities. A comparison of our simulation results with the model shows that heterogeneous classical nucleation theory provides a good estimate of the critical size of the film but significantly over-estimates the size of the barrier.Comment: 9 pages, 10 figures, In Print J. Chem. Phy

Crystal nucleation and cluster-growth kinetics in a model glass under shear

Crystal nucleation and growth processes induced by an externally applied shear strain in a model metallic glass are studied by means of nonequilibrium molecular dynamics simulations, in a range of temperatures. We observe that the nucleation-growth process takes place after a transient, induction regime. The critical cluster size and the lag-time associated with this induction period are determined from a mean first-passage time analysis. The laws that describe the cluster growth process are studied as a function of temperature and strain rate. A theoretical model for crystallization kinetics that includes the time dependence for nucleation and cluster growth is developed within the framework of the Kolmogorov-Johnson-Mehl-Avrami scenario and is compared with the molecular dynamics data. Scalings for the cluster growth laws and for the crystallization kinetics are also proposed and tested. The observed nucleation rates are found to display a nonmonotonic strain rate dependency

Nucleation in scale-free networks

We have studied nucleation dynamics of the Ising model in scale-free networks with degree distribution $P(k)\sim k^{-\gamma}$ by using forward flux sampling method, focusing on how the network topology would influence the nucleation rate and pathway. For homogeneous nucleation, the new phase clusters grow from those nodes with smaller degree, while the cluster sizes follow a power-law distribution. Interestingly, we find that the nucleation rate $R_{Hom}$ decays exponentially with the network size $N$, and accordingly the critical nucleus size increases linearly with $N$, implying that homogeneous nucleation is not relevant in the thermodynamic limit. These observations are robust to the change of $\gamma$ and also present in random networks. In addition, we have also studied the dynamics of heterogeneous nucleation, wherein $w$ impurities are initially added, either to randomly selected nodes or to targeted ones with largest degrees. We find that targeted impurities can enhance the nucleation rate $R_{Het}$ much more sharply than random ones. Moreover, $\ln (R_{Het}/R_{Hom})$ scales as $w^{\gamma-2/\gamma-1}$ and $w$ for targeted and random impurities, respectively. A simple mean field analysis is also present to qualitatively illustrate above simulation results.Comment: 7 pages, 5 figure

A dynamical theory of homogeneous nucleation for colloids and macromolecules

Homogeneous nucleation is formulated within the context of fluctuating hydrodynamics. It is shown that for a colloidal or macromolecular system in the strong damping limit the most likely path for nucleation can be determined by gradient descent in density space governed by a nontrivial metric fixed by the dynamics. The theory provides a justification and extension of more heuristic equilibrium approaches based solely on the free energy. It is illustrated by application to liquid-vapor nucleation where it is shown that, in contrast to most free energy-based studies, the smallest clusters correspond to long wavelength, small amplitude perturbations.Comment: final version; 4 pages, 2 figure

Systematic Improvement of Classical Nucleation Theory

We reconsider the applicability of classical nucleation theory (CNT) to the calculation of the free energy of solid cluster formation in a liquid and its use to the evaluation of interface free energies from nucleation barriers. Using two different freezing transitions (hard spheres and NaCl) as test cases, we first observe that the interface-free-energy estimates based on CNT are generally in error. As successive refinements of nucleation-barrier theory, we consider corrections due to a non-sharp solid-liquid interface and to a non-spherical cluster shape. Extensive calculations for the Ising model show that corrections due to a non-sharp and thermally fluctuating interface account for the barrier shape with excellent accuracy. The experimental solid nucleation rates that are measured in colloids are better accounted for by these non-CNT terms, whose effect appears to be crucial in the interpretation of data and in the extraction of the interface tension from them.Comment: 20 pages (text + supplementary material

Modeling of Nucleation Processes

Nucleation is the onset of a first-order phase transition by which a metastable phase transforms into a more stable one. Such a phase transition occurs when an initial system initially in equilibrium is destabilized by the change of an external parameter like the temperature or the pressure. If the perturbation is small enough, the system does not become unstable but rather stays metastable. In diffusive transformations, the system then evolves through the nucleation, the growth and the coarsening of a second phase. Such a phase transformation is found in a lot of situations in materials science like condensation of liquid droplets from a supersaturated vapor, solidification, precipitation from a supersaturated solid solution, ... The initial stage of all these different processes can be well described within the same framework. Since its initial formulation in 1927 by Volmer, Weber and Farkas and its modification in 1935 by Becker and D\"oring the classical nucleation theory has been a suitable tool to model the nucleation stage in phase transformations. In this article, we first describe this theory. A kinetic approach, the cluster dynamics, can also be used to describe nucleation. This constitutes the second part of this article. The links as well as the difference between both descriptions are emphasized. Since its initial formulation, the classical nucleation theory has been enriched, so as to take into account the fact that clusters other than monomers can migrate and react. It has been also extended to multi-component systems. These generalizations of the initial formalism are also presented