Activity affects the stability, deformation and breakage dynamics of colloidal architectures.

Living network architectures, such as the cytoskeleton, are characterized by continuous energy injection, leading to rich but poorly understood non-equilibrium physics. There is a need for a well-controlled (experimental) model system that allows basic insight into such non-equilibrium processes. Activated self-assembled colloidal architectures can fulfill this role, as colloidal patchy particles can self-assemble into colloidal architectures such as chains, rings and networks, while self-propelled colloidal particles can simultaneously inject energy into the architecture, alter the dynamical behavior of the system, and cause the self-assembled structures to deform and break. To gain insight, we conduct a numerical investigation into the effect of introducing self-propelled colloids modeled as active Brownian particles, into self-assembling colloidal dispersions of dipatch and tripatch particles. For the interaction potential, we use a previously designed model that accurately can reproduce experimental colloidal self-assembly via the critical Casimir force [Jonas et al., J. Chem. Phys., 2021, 135, 034902]. Here, we focus primarily on the breakage dynamics of three archetypal substructures, namely, dimers, chains, and rings. We find a rich response behavior to the introduction of self-propelled particles, in which the activity can enhance as well as reduce the stability of the architecture, deform the intact structures and alter the mechanisms of fragmentation. We rationalize these findings in terms of the rate and mechanisms of breakage as a function of the direction and magnitude of the active force by separating the bond breakage process into two stages: escaping the potential well and separation of the particles. The results set the stage for investigating more complex architectures.

Extended Wertheim theory predicts the anomalous chain length distributions of divalent patchy particles under extreme confinement.

Colloidal patchy particles with divalent attractive interaction can self-assemble into linear polymer chains. Their equilibrium properties in 2D and 3D are well described by Wertheim's thermodynamic perturbation theory, which predicts a well-defined, exponentially decaying equilibrium chain length distribution. In experimental realizations, due to gravity, particles sediment to the bottom of the suspension, forming a monolayer of particles with a gravitational height smaller than the particle diameter. In accordance with experiments, an anomalously high monomer concentration is observed in simulations, which is not well understood. To account for this observation, we interpret polymerization as taking place in a highly confined quasi-2D plane and extend the Wertheim thermodynamic perturbation theory by defining additional reaction constants as functions of chain length. We derive the theory, test it on simple square well potentials, and apply it to the experimental case of synthetic colloidal patchy particles immersed in a binary liquid mixture, which are described by an accurate effective critical Casimir patchy particle potential. The important interaction parameters entering the theory are explicitly computed using the integral method in combination with Monte Carlo sampling. Without any adjustable parameter, the predictions of the chain length distribution are in excellent agreement with explicit simulations of self-assembling particles. We discuss the generality of the approach and its application range.

An extended autoencoder model for reaction coordinate discovery in rare event molecular dynamics datasets.

The reaction coordinate (RC) is the principal collective variable or feature that determines the progress along an activated or reactive process. In a molecular simulation using enhanced sampling, a good description of the RC is crucial for generating sufficient statistics. Moreover, the RC provides invaluable atomistic insight into the process under study. The optimal RC is the committor, which represents the likelihood of a system to evolve toward a given state based on the coordinates of all its particles. As the interpretability of such a high dimensional function is low, a more practical approach is to describe the RC by some low-dimensional molecular collective variables or order parameters. While several methods can perform this dimensionality reduction, they usually require a preselection of these low-dimension collective variables (CVs). Here, we propose to automate this dimensionality reduction using an extended autoencoder, which maps the input (many CVs) onto a lower-dimensional latent space, which is subsequently used for the reconstruction of the input as well as the prediction of the committor function. As a consequence, the latent space is optimized for both reconstruction and committor prediction and is likely to yield the best non-linear low-dimensional representation of the committor. We test our extended autoencoder model on simple but nontrivial toy systems, as well as extensive molecular simulation data of methane hydrate nucleation. The extended autoencoder model can effectively extract the underlying mechanism of a reaction, make reliable predictions about the committor of a given configuration, and potentially even generate new paths representative for a reaction.

A temperature-dependent critical Casimir patchy particle model benchmarked onto experiment.

Synthetic colloidal patchy particles immersed in a binary liquid mixture can self-assemble via critical Casimir interactions into various superstructures, such as chains and networks. Up to now, there are no quantitatively accurate potential models that can simulate and predict this experimentally observed behavior precisely. Here, we develop a protocol to establish such a model based on a combination of theoretical Casimir potentials and angular switching functions. Using Monte Carlo simulations, we optimize several material-specific parameters in the model to match the experimental chain length distribution and persistence length. Our approach gives a systematic way to obtain accurate potentials for critical Casimir induced patchy particle interactions and can be used in large-scale simulations.

Revealing pseudorotation and ring-opening reactions in colloidal organic molecules.

Colloids have a rich history of being used as 'big atoms' mimicking real atoms to study crystallization, gelation and the glass transition of condensed matter. Emulating the dynamics of molecules, however, has remained elusive. Recent advances in colloid chemistry allow patchy particles to be synthesized with accurate control over shape, functionality and coordination number. Here, we show that colloidal alkanes, specifically colloidal cyclopentane, assembled from tetrameric patchy particles by critical Casimir forces undergo the same chemical transformations as their atomic counterparts, allowing their dynamics to be studied in real time. We directly observe transitions between chair and twist conformations in colloidal cyclopentane, and we elucidate the interplay of bond bending strain and entropy in the molecular transition states and ring-opening reactions. These results open the door to investigate complex molecular kinetics and molecular reactions in the high-temperature classical limit, in which the colloidal analogue becomes a good model.

Molecular Understanding of Homogeneous Nucleation of CO2 Hydrates Using Transition Path Sampling.

Carbon dioxide hydrate is a solid built from hydrogen-bond stabilized water cages that encapsulate individual CO2 molecules. As potential candidates for reducing greenhouse gases, hydrates have attracted attention from both the industry and scientific community. Under high pressure and low temperature, hydrates are formed spontaneously from a mixture of CO2 and water via nucleation and growth. Yet, for moderate undercooling, i.e., moderate supersaturation, studying hydrate formation with molecular simulations is very challenging due to the high nucleation barriers involved. We investigate the homogeneous nucleation mechanism of CO2 hydrate as a function of temperature using transition path sampling (TPS), which generates ensembles of unbiased dynamical trajectories across the high barrier between the liquid and solid states. The resulting path ensembles reveal that at high driving force (low temperature), amorphous structures are predominantly formed, with 4151062 cages being the most abundant. With increasing temperature, the nucleation mechanism changes, and 51262 becomes the most abundant cage type, giving rise to the crystalline sI structure. Reaction coordinate analysis can reveal the most important collective variable involved in the mechanism. With increasing temperature, we observe a shift from a single feature (size of the nucleus) to a 2-dimensional (size and cage type) variable as the salient ingredient of the reaction coordinate, and then back to only the nucleus size. This finding is in line with the underlying shift from an amorphous to a crystalline nucleation channel. Modeling such complex phase transformations using transition path sampling gives unbiased insight into the molecular mechanisms toward different polymorphs, and how these are determined by thermodynamics and kinetics. This study will be beneficial for researchers aiming to produce such hydrates with different polymorphic forms.

Rate Prediction for Homogeneous Nucleation of Methane Hydrate at Moderate Supersaturation Using Transition Interface Sampling.

The crystallization of methane hydrates via homogeneous nucleation under natural, moderate conditions is of both industrial and scientific relevance, yet still poorly understood. Predicting the nucleation rates at such conditions is notoriously difficult due to high nucleation barriers, and requires, besides an accurate molecular model, enhanced sampling. Here, we apply the transition interface sampling technique, which efficiently computes the exact rate of nucleation by generating ensembles of unbiased dynamical trajectories crossing predefined interfaces located between the stable states. Using an accurate atomistic force field and focusing on specific conditions of 280 K and 500 bar, we compute for nucleation directly into the sI crystal phase at a rate of ∼10-17 nuclei per nanosecond per simulation volume or ∼102 nuclei per second per cm3, in agreement with consensus estimates for nearby conditions. As this is most likely fortuitous, we discuss the causes of the large differences between our results and previous simulation studies. Our work shows that it is now possible to compute rates for methane hydrates at moderate supersaturation, without relying on any assumptions other than the force field.

Transition path sampling for non-equilibrium dynamics without predefined reaction coordinates.

We develop two novel transition path sampling (TPS) algorithms for harvesting ensembles of rare event trajectories using non-equilibrium dynamics. These methods have the advantage that no predefined reaction coordinate is needed. Instead, an instantaneous reaction coordinate is based on the current path. Constituting a Monte Carlo random walk in trajectory space, the algorithms can be viewed as bridging between the original TPS methodology and the Rosenbluth based forward flux sampling methodology. We illustrate the new methods on toy models undergoing equilibrium and non-equilibrium dynamics, including an active Brownian particle system. For the latter, we find that transitions between steady states occur via states that are locally ordered but globally disordered.

Unbiased Atomistic Insight into the Mechanisms and Solvent Role for Globular Protein Dimer Dissociation.

Association and dissociation of proteins are fundamental processes in nature. Although simple to understand conceptually, the details of the underlying mechanisms and role of the solvent are poorly understood. Here, we investigate the dissociation of the hydrophilic ß-lactoglobulin dimer by employing transition path sampling. Analysis of the sampled path ensembles reveals a variety of mechanisms: (1) a direct aligned dissociation (2) a hopping and rebinding transition followed by unbinding, and (3) a sliding transition before unbinding. Reaction coordinate and transition-state analysis predicts that, besides native contact and neighboring salt-bridge interactions, solvent degrees of freedom play an important role in the dissociation process. Bridging waters, hydrogen-bonded to both proteins, support contacts in the native state and nearby lying transition-state regions, whereas they exhibit faster dynamics in further lying transition-state regions, rendering the proteins more mobile and assisting in rebinding. Analysis of the structure and dynamics of the solvent molecules reveals that the dry native interface induces enhanced populations of both disordered hydration water near hydrophilic residues and tetrahedrally ordered hydration water nearby hydrophobic residues. Although not exhaustive, our sampling of rare unbiased reactive molecular dynamics trajectories enhances the understanding of protein dissociation via complex pathways including (multiple) rebinding events.

Dynamics of Hydration Water around Native and Misfolded α-Lactalbumin.

As water is an essential ingredient in protein structure, dynamics, and functioning, knowledge of its behavior near proteins is crucial. We investigate water dynamics around bovine α-lactalbumin by combining molecular dynamics simulations with polarization-resolved femtosecond infrared (fs-IR) spectroscopy. We identify slowly reorienting surface waters and establish their hydrogen-bond lifetime and reorientation dynamics, which we compare to the experimentally measured anisotropy decay. The calculated number of slow surface waters is in reasonable agreement with the results of fs-IR experiments. While surface waters form fewer hydrogen bonds than the bulk, within the hydration layer water is slower when donating more hydrogen bonds. At concave sites the protein-water hydrogen bonds break preferably via translational diffusion rather than via a hydrogen-bond jump mechanism. Water molecules reorient slower near these sites than at convex water-exposed sites. Protein misfolding leads to an increased exposure of hydrophobic groups, inducing relatively faster surface water dynamics. Nevertheless, the larger exposed surface slows down a larger amount of water. While for native proteins hydrating water is slower near hydrophobic than near hydrophilic residues, mainly due to stronger confinement, misfolding causes hydrophobic water to reorient relatively faster because exposure of hydrophobic groups destroys concave protein cavities with a large excluded volume.

Phase transition to bundles of flexible supramolecular polymers.

We report Monte Carlo simulations of the self-assembly of supramolecular polymers based on a model of patchy particles. We find a first-order phase transition, characterized by hysteresis and nucleation, toward a solid bundle of polymers, of length much greater than the average gas phase length. We argue that the bundling transition is the supramolecular equivalent of the sublimation transition, which results from a weak chain-chain interaction. We provide a qualitative equation of state that gives physical insight beyond the specific values of the parameters used in our simulations.

Sampling the multiple folding mechanisms of Trp-cage in explicit solvent.

We investigate the kinetic pathways of folding and unfolding of the designed miniprotein Trp- cage in explicit solvent. Straightforward molecular dynamics and replica exchange methods both have severe convergence problems, whereas transition path sampling allows us to sample unbiased dynamical pathways between folded and unfolded states and leads to deeper understanding of the mechanisms of (un)folding. In contrast to previous predictions employing an implicit solvent, we find that Trp-cage folds primarily (80% of the paths) via a pathway forming the tertiary contacts and the salt bridge, before helix formation. The remaining 20% of the paths occur in the opposite order, by first forming the helix. The transition states of the rate-limiting steps are solvated native-like structures. Water expulsion is found to be the last step upon folding for each route. Committor analysis suggests that the dynamics of the solvent is not part of the reaction coordinate. Nevertheless, during the transition, specific water molecules are strongly bound and can play a structural role in the folding.

Influence of polymer-excluded volume on the phase-behavior of colloid-polymer mixtures.

We determine the depletion-induced phase-behavior of hard-sphere colloids and interacting polymers by large-scale Monte Carlo simulations using very accurate coarse-graining techniques. A comparison with standard Asakura-Oosawa model theories and simulations shows that including excluded-volume interactions between polymers leads to qualitative differences in the phase diagrams. These effects become increasingly important for larger relative polymer size. Our simulation results agree quantitatively with recent experiments.

Many-body interactions and correlations in coarse-grained descriptions of polymer solutions.

We calculate the two-, three-, four-, and five-body (state-independent) effective potentials between the centers of mass (c.m.'s) of self-avoiding walk polymers by Monte Carlo simulations. For full overlap, these coarse-grained n-body interactions oscillate in sign as (-1)(n), and decrease in absolute magnitude with increasing n. We find semiquantitative agreement with a scaling theory, and use this to discuss how the coarse-grained free energy converges when expanded to arbitrary order in the many-body potentials. We also derive effective density dependent two-body potentials that exactly reproduce the pair-correlations between the c.m. of the self avoiding walk polymers. The density dependence of these pair potentials can be largely understood from the effects of the density independent three-body potential. Triplet correlations between the c.m. of the polymers are surprisingly well, but not exactly, described by our coarse-grained effective pair potential picture. In fact, we demonstrate that a pair potential cannot simultaneously reproduce the two- and three-body correlations in a system with many-body interactions. However, the deviations that do occur in our system are very small, and can be explained by the direct influence of three-body potentials.

Reaction coordinates of biomolecular isomerization.

Transition path sampling has been applied to the molecular dynamics of the alanine dipeptide in vacuum and in aqueous solution. The analysis shows that more degrees of freedom than the traditional dihedral angles, phi and psi, are necessary to describe the reaction coordinates for isomerization of this molecule. In vacuum, an additional dihedral angle is identified as significant. In solution, solvent variables are shown to play a significant role, and this role appears to be more specific than can be captured by friction models. Implications for larger molecules are discussed.