arXiv subjects

Glen M. Hocky

Publications and source records attributed to Glen M. Hocky.

25 records · Page 2Linked to original sources

arXiv2019

Infinite Switch Simulated Tempering in Force (FISST)

Many proteins in cells are capable of sensing and responding to piconewton scale forces, a regime in which conformational changes are small but significant for biological processes. In order to efficiently and effectively sample the response of these proteins to small forces, enhanced sampling techniques will be required. In this work, we derive, implement, and evaluate an efficient method to simultaneously sample the result of applying any constant pulling force within a specified range to a molecular system of interest. We start from Simulated Tempering in Force, whereby force is applied as a linear bias on a collective variable to the system's Hamiltonian, and the coefficient is taken as a continuous auxiliary degree of freedom. We derive a formula for an average collective-variable-dependent force, which depends on a set of weights, learned on-the-fly throughout a simulation, that reflect the limit where force varies infinitely quickly. These weights can then be used to retroactively compute averages of any observable at any force within the specified range. This technique is based on recent work deriving similar equations for Infinite Switch Simulated Tempering in Temperature, that showed the infinite switch limit is the most efficient for sampling. Here, we demonstrate that our method accurately and simultaneously samples molecular systems at all forces within a user defined force range, and show how it can serve as an enhanced sampling tool for cases where the pulling direction destabilizes states of low free-energy at zero-force. This method is implemented in, and will be freely-distributed with, the PLUMED open-source sampling library, and hence can be readily applied to problems using a wide range of molecular dynamics software packages.

cond-mat.stat-mech↗

arXiv2018

Design principles for selective self-assembly of active networks

Living cells dynamically modulate the local morphologies of their actin cytoskeletons to perform biological functions, including force transduction, intracellular transport, and cell division. A major challenge is to understand how diverse structures of the actin cytoskeleton are assembled from a limited set of molecular building blocks. Here we study the spontaneous self-assembly of a minimal model of cytoskeletal materials, consisting of semiflexible actin filaments, crosslinkers, and molecular motors. Using coarse-grained simulations, we demonstrate that by changing concentrations and kinetics of crosslinkers and motors we can generate three distinct structural phases of actomyosin assemblies: bundled, polarity-sorted, and contracted. We introduce new metrics to distinguish these structural phases and demonstrate their functional roles. We find that the binding kinetics of motors and crosslinkers can be tuned to optimize contractile force generation, motor transport, and mechanical response. By quantitatively characterizing the relationships between modes of cytoskeletal self-assembly, the resulting structures, and their functional consequences, our work suggests new principles for the design of active materials.

physics.bio-ph↗

arXiv2017

A versatile framework for simulating the dynamic mechanical structure of cytoskeletal networks

Computer simulations can aid in understanding how collective materials properties emerge from interactions between simple constituents. Here, we introduce a coarse-grained model that enables simulation of networks of actin filaments, myosin motors, and crosslinking proteins at biologically relevant time and length scales. We demonstrate that the model qualitatively and quantitatively captures a suite of trends observed experimentally, including the statistics of filament fluctuations, mechanical responses to shear, motor motilities, and network rearrangements. We use the simulation to predict the viscoelastic scaling behavior of crosslinked actin networks, characterize the trajectories of actin in a myosin motility assay, and develop order parameters to measure contractility of a simulated actin network. The model can thus serve as a platform for interpretation and design of cytoskeletal materials experiments, as well as for further development of simulations incorporating active elements.

physics.bio-ph↗

arXiv2017

Improved Ab Initio Molecular Dynamics by Minimal Biasing with Experimental Data

Accounting for electrons and nuclei simultaneously is a powerful capability of ab initio molecular dynamics (AIMD). However, AIMD is often unable to accurately reproduce properties of systems such as water due to inaccuracies in the underlying electronic density functionals. This shortcoming is often addressed by added empirical corrections and/or increasing the simulation temperature. We present here a maximum-entropy approach to directly incorporate limited experimental data via a minimal bias. Biased AIMD simulations of water and an excess proton in water are shown to give significantly improved properties both for observables which were biased to match experimental data and for unbiased observables. This approach also yields new physical insight into inaccuracies in the underlying density functional theory as utilized in the unbiased AIMD.

physics.chem-ph↗

arXiv2014

Correlation of Local Order with Particle Mobility in Supercooled Liquids is Highly System Dependent

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.

cond-mat.stat-mech↗

arXiv2013

A small subset of normal modes mimics the properties of dynamical heterogeneity in a model supercooled liquid

In this work, we study the nature of transitions between inherent structures of a two-dimensional model supercooled liquid. We demonstrate that these transitions occur predominately along a small number of directions on the energy landscape. Moreover, we show that the number of such directions decreases as the temperature of the liquid is decreased in the mildly supercooled regime, in concert with earlier studies on an athermal jamming system. We show that this decrease happens in parallel with a change in character of the transitions as dynamics in the system become more heterogeneous and localized. We investigate the origin of these trends, which suggests interesting connections between jamming and thermal glassy phenomena.

cond-mat.stat-mech↗

arXiv2012

Growing point-to-set length scale correlates with growing relaxation times in model supercooled liquids

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.

cond-mat.stat-mech↗