Protein folding on rugged energy landscapes: Conformational diffusion on fractal networks

We employ simulations of model proteins to study folding on rugged energy landscapes. We construct ``first-passage'' networks as the system transitions from unfolded to native states. The nodes and bonds in these networks correspond to basins and transitions between them in the energy landscape. We find power-laws between the folding time and number of nodes and bonds. We show that these scalings are determined by the fractal properties of first-passage networks. Reliable folding is possible in systems with rugged energy landscapes because first passage networks have small fractal dimension.Comment: 4 pages, 6 figure

Experiments demonstrate that the null space of the rigidity matrix determines grain motion during vibration-induced compaction

Using a previously developed experimental method to reduce friction in mechanically stable packings of disks, we find that frictional packings form tree-like structures of geometrical families that lie on reduced dimensional manifolds in configuration space. Each branch of the tree begins at a point in configuration space with an isostatic number of contacts and spreads out to sequentially higher dimensional manifolds as the number of contacts are reduced. We find that gravitational deposition of disks produces an initially under-coordinated packing stabilized by friction on a high-dimensional manifold. Using short vibration bursts to reduce friction, we compact the system through many stable configurations with increasing contact number and decreasing dimensionality until the system reaches an isostatic frictionless state. We find that this progression can be understood as the system moving through the null-space of the rigidity matrix defined by the interparticle contact network in the direction of the gravitational force. We suggest that this formalism can also be used to explain the evolution of frictional packings under other forcing conditions.Comment: 5 pages, 3 figure

Quasi-One Dimensional Models for Glassy Dynamics

We describe numerical simulations and analyses of a quasi-one-dimensional (Q1D) model of glassy dynamics. In this model, hard rods undergo Brownian dynamics through a series of narrow channels connected by $J$ intersections. We do not allow the rods to turn at the intersections, and thus there is a single, continuous route through the system. This Q1D model displays caging behavior, collective particle rearrangements, and rapid growth of the structural relaxation time, which are also found in supercooled liquids and glasses. The mean-square displacement $\Sigma(t)$ for this Q1D model displays several dynamical regimes: 1) short-time diffusion $\Sigma(t) \sim t$, 2) a plateau in the mean-square displacement caused by caging behavior, 3) single-file diffusion characterized by anomalous scaling $\Sigma(t) \sim t^{0.5}$ at intermediate times, and 4) a crossover to long-time diffusion $\Sigma(t) \sim t$ for times $t$ that grow with the complexity of the circuit. We develop a general procedure for determining the structural relaxation time $t_D$, beyond which the system undergoes long-time diffusion, as a function of the packing fraction $\phi$ and system topology. This procedure involves several steps: 1) define a set of distinct microstates in configuration space of the system, 2) construct a directed network of microstates and transitions between them, 3) identify minimal, closed loops in the network that give rise to structural relaxation, 4) determine the frequencies of `bottleneck' microstates that control the slow dynamics and time required to transition out of them, and 5) use the microstate frequencies and lifetimes to deduce $t_D(\phi)$. We find that $t_D$ obeys power-law scaling, $t_D\sim (\phi^* - \phi)^{-\alpha}$, where both $\phi^*$ (signaling complete kinetic arrest) and $\alpha>0$ depend on the system topology.Comment: 16 pages, 18 figure

The contact percolation transition

Typical quasistatic compression algorithms for generating jammed packings of athermal, purely repulsive particles begin with dilute configurations and then apply successive compressions with relaxation of the elastic energy allowed between each compression step. It is well-known that during isotropic compression athermal systems with purely repulsive interactions undergo a jamming transition at packing fraction $\phi_J$ from an unjammed state with zero pressure to a jammed, rigid state with nonzero pressure. Using extensive computer simulations, we show that a novel second-order-like transition, the contact percolation transition, which signals the formation of a system-spanning cluster of mutually contacting particles, occurs at $\phi_P < \phi_J$, preceding the jamming transition. By measuring the number of non-floppy modes of the dynamical matrix, and the displacement field and time-dependent pressure following compression, we find that the contact percolation transition also heralds the onset of complex spatiotemporal response to applied stress. Thus, highly heterogeneous, cooperative, and non-affine particle motion occurs in unjammed systems significantly below the jamming transition for $\phi_P < \phi < \phi_J$, not only for jammed systems with $\phi > \phi_J$.Comment: 4 pages, 4 figure

Glassy dynamics of crystallite formation: The role of covalent bonds

We examine nonequilibrium features of collapse behavior in model polymers with competing crystallization and glass transitions using extensive molecular dynamics simulations. By comparing to "colloidal" systems with no covalent bonds but the same non-bonded interactions, we find three principal results: (i) Tangent-sphere polymers and colloids, in the equilibrium-crystallite phase, have nearly identical static properties when the temperature T is scaled by the crystallization temperature T_{cryst}; (ii) Qualitative features of nonequilibrium relaxation below T_{cryst}, measured by the evolution of local structural properties (such as the number of contacts) toward equilibrium crystallites, are the same for polymers and colloids; and (iii) Significant quantitative differences in rearrangements in polymeric and colloidal crystallites, in both far-from equilibrium and near-equilibrium systems, can be understood in terms of chain connectivity. These results have important implications for understanding slow relaxation processes in collapsed polymers, partially folded, misfolded, and intrinsically disordered proteins.Comment: The manuscript has been extensively revised for clarity, 2 additional system sizes are considered to validate trends, and the timescale of nonequilibrium aging simulations has been extended by a factor of 5. 13 pages, 8 figures, RSC styl

Minimal energy packings of nearly flexible polymers

We extend recent studies of the minimal energy packings of short flexible polymers with hard-core-like repulsions and short-range attractions to include bond-angle interactions with the aim of describing the collapsed conformations of `colloidal' polymers. We find that flexible tangent sticky-hard-sphere (t-SHS) packings provide a useful perturbative basis for analyzing polymer packings with nonzero bending stiffness only for {\it small} ratios of the stiffnesses for the bond-angle ($k_b$) and pair ($k_c$) interactions, i.e. $k_b^{\rm crit}/k_c \lesssim 0.01$ for $N<10$ monomers, and the critical ratio decreases with $N$. Below $k_b^{crit}$, angular interactions give rise to an exponential (in $N$) increase in the number of distinct angular energies arising from the diversity of covalent backbone paths through t-SHS packings. As $k_b$ increases above $k_b^{crit}$, the low-lying energy landscape changes dramatically as finite bending stiffness alters the structure of the polymer packings. This study lays the groundwork for exact-enumeration studies of the collapsed states of t-SHS-like models with larger bending stiffness.Comment: accepted for publication in J. Chem. Phy

Vibrations of Jammed Disk Packings with Hertzian Interactions

Contact breaking and Hertzian interactions between grains can both give rise to nonlinear vibrational response of static granular packings. We perform molecular dynamics simulations at constant energy in 2D of frictionless bidisperse disks that interact via Hertzian spring potentials as a function of energy and measure directly the vibrational response from the Fourier transform of the velocity autocorrelation function. We compare the measured vibrational response of static packings near jamming onset to that obtained from the eigenvalues of the dynamical matrix to determine the temperature above which the linear response breaks down. We compare packings that interact via single-sided (purely repulsive) and double-sided Hertzian spring interactions to disentangle the effects of the shape of the potential from contact breaking. Our studies show that while Hertzian interactions lead to weak nonlinearities in the vibrational behavior (e.g. the generation of harmonics of the eigenfrequencies of the dynamical matrix), the vibrational response of static packings with Hertzian contact interactions is dominated by contact breaking as found for systems with repulsive linear spring interactions.Comment: 8 pages, 6 figure

Void distributions reveal structural link between jammed packings and protein cores

Dense packing of hydrophobic residues in the cores of globular proteins determines their stability. Recently, we have shown that protein cores possess packing fraction $\phi \approx 0.56$, which is the same as dense, random packing of amino acid-shaped particles. In this article, we compare the structural properties of protein cores and jammed packings of amino acid-shaped particles in much greater depth by measuring their local and connected void regions. We find that the distributions of surface Voronoi cell volumes and local porosities obey similar statistics in both systems. We also measure the probability that accessible, connected void regions percolate as a function of the size of a spherical probe particle and show that both systems possess the same critical probe size. By measuring the critical exponent $\tau$ that characterizes the size distribution of connected void clusters at the onset of percolation, we show that void percolation in packings of amino acid-shaped particles and protein cores belong to the same universality class, which is different from that for void percolation in jammed sphere packings. We propose that the connected void regions of proteins are a defining feature of proteins and can be used to differentiate experimentally observed proteins from decoy structures that are generated using computational protein design software. This work emphasizes that jammed packings of amino acid-shaped particles can serve as structural and mechanical analogs of protein cores, and could therefore be useful in modeling the response of protein cores to cavity-expanding and -reducing mutations.Comment: 14 pages, 11 figure

The response of jammed packings to thermal fluctuations

We focus on the response of mechanically stable (MS) packings of frictionless, bidisperse disks to thermal fluctuations, with the aim of quantifying how nonlinearities affect system properties at finite temperature. Packings of disks with purely repulsive contact interactions possess two main types of nonlinearities, one from the form of the interaction potential and one from the breaking (or forming) of interparticle contacts. To identify the temperature regime at which the contact-breaking nonlinearities begin to contribute, we first calculated the minimum temperatures $T_{cb}$ required to break a single contact in the MS packing for both single and multiple eigenmode perturbations of the $T=0$ MS packing. We then studied deviations in the constant volume specific heat $C_V$ and deviations of the average disk positions $\Delta r$ from their $T=0$ values in the temperature regime $T_{cb} < T < T_{r}$, where $T_r$ is the temperature beyond which the system samples the basin of a new MS packing. We find that the deviation in the specific heat per particle $\Delta {\overline C}_V^0/{\overline C}_V^0$ relative to the zero temperature value ${\overline C}_V^0$ can grow rapidly above $T_{cb}$, however, the deviation $\Delta {\overline C}_V^0/{\overline C}_V^0$ decreases as $N^{-1}$ with increasing system size. To characterize the relative strength of contact-breaking versus form nonlinearities, we measured the ratio of the average position deviations $\Delta r^{ss}/\Delta r^{ds}$ for single- and double-sided linear and nonlinear spring interactions. We find that $\Delta r^{ss}/\Delta r^{ds} > 100$ for linear spring interactions and is independent of system size.Comment: 15 pages, 13 figure

Response to Comment on Repulsive contact interactions make jammed particulate systems inherently nonharmonic'

This is a response to the comment on our manuscript "Repulsive contact interactions make jammed particulate systems inherently nonharmonic" (Physical Review Letters 107 (2011) 078301) by C. P. Goodrich, A. J. Liu, and S. R. Nagel.Comment: 6 pages, 1 figur