Gaurav Arya | University of California, San Diego (original) (raw)

Papers by Gaurav Arya

Publikationsansicht. 31077273. Molecular simulation of transport in nanoporous materials / (2003)... more Publikationsansicht. 31077273. Molecular simulation of transport in nanoporous materials / (2003). Arya, Gaurav. Abstract. Thesis (Ph. D.)--University of Notre Dame, 2003.. Thesis directed by Edward J. Maginn and Hsueh-Chia ...

Nucleic Acids Research, 2015

Hi-C experiments produce large numbers of DNA sequence read pairs that are typically analyzed to ... more Hi-C experiments produce large numbers of DNA sequence read pairs that are typically analyzed to deduce genomewide interactions between arbitrary loci. A key step in these experiments is the cleavage of cross-linked chromatin with a restriction endonuclease. Although this cleavage should happen specifically at the enzyme's recognition sequence, an unknown proportion of cleavage events may involve other sequences, owing to the enzyme's star activity or to random DNA breakage. A quantitative estimation of these non-specific cleavages may enable simulating realistic Hi-C read pairs for validation of downstream analyses, monitoring the reproducibility of experimental conditions and investigating biophysical properties that correlate with DNA cleavage patterns. Here we describe a computational method for analyzing Hi-C read pairs to estimate the fractions of cleavages at different possible targets. The method relies on expressing an observed local target distribution downstream of aligned reads as a linear combination of known conditional local target distributions. We validated this method using Hi-C read pairs obtained by computer simulation. Application of the method to experimental Hi-C datasets from murine cells revealed interesting similarities and differences in patterns of cleavage across the various experiments considered.

A clear understanding of the molecular mechanisms responsible for energy and shock dissipation in... more A clear understanding of the molecular mechanisms responsible for energy and shock dissipation in elastomeric materials is essential for the design of next-generation materials for blast mitigation. Even though current high-end, protective gear typically rely on polyurea and polyurea-based materials for protection against blasts, the molecular basis for the dissipative properties of polyurea remains unknown. It may be hypothesized that the multiblock chain architecture of polyurea--repeating units of hard and soft segments--might be partly responsible for its superior dissipative properties. As a first step towards addressing this question, we carry out a detailed comparison of the microstructure, viscoelastic properties, and shock response of coarse-grained models of multiblock and diblock copolymers using molecular dynamics simulations. We find that the multiblock copolymer forms small, interconnected, rod-shaped, hard domains surrounded by a soft matrix, whereas the diblock copol...

Biophysical Journal, 2014

Journal of Biomolecular Structure and Dynamics, 2015

While considerable attempts have been made to recreate the high turnover rates of enzymes using s... more While considerable attempts have been made to recreate the high turnover rates of enzymes using synthetic enzyme mimics, most have failed and only a few have produced minimal reaction rates that can barely be considered catalytic. One particular approach we have focused on is the use of short-sequence peptides that contain key catalytic groups in close proximity. In this study, we designed six different peptides and tested their ability to mimic the catalytic mechanism of the cysteine proteases. Acetylation and deacylation by Ellman&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s Reagent trapping experiments showed the importance of having phenylalanine groups surrounding the catalytic sites in order to provide greater proximity between the cysteine, histidine, and aspartate amino acid R-groups. We have also carried out all-atom molecular dynamics simulations to determine the distance between these catalytic groups and the overall mechanical flexibility of the peptides. We found strong correlations between the magnitude of fluctuations in the Cys-His distance, which determines the flexibility and interactions between the cysteine thiol and histidine imidazole groups, and the deacylation rate. We found that, in general, shorter Cys-His distance fluctuations led to a higher deacylation rate constant, implying that greater confinement of the two residues will allow a higher frequency of the acetyl exchange between the cysteine thiol and histidine imidazole R-groups. This may be the key to future design of peptide structures with molecular mechanical properties that lead to viable enzyme mimics.

Nucleic acids research, 2014

Torsionally stressed DNA plays a critical role in genome organization and regulation. While the e... more Torsionally stressed DNA plays a critical role in genome organization and regulation. While the effects of torsional stresses on naked DNA have been well studied, little is known about how these stresses propagate within chromatin and affect its organization. Here we investigate the torsional behavior of nucleosome arrays by means of Brownian dynamics simulations of a coarse-grained model of chromatin. Our simulations reveal a strong dependence of the torsional response on the rotational phase angle Ψ0 between adjacent nucleosomes. Extreme values of Ψ0 lead to asymmetric, bell-shaped extension-rotation profiles with sharp maxima shifted toward positive or negative rotations, depending on the sign of Ψ0, and to fast, irregular propagation of DNA twist. In contrast, moderate Ψ0 yield more symmetric profiles with broad maxima and slow, uniform propagation of twist. The observed behavior is shown to arise from an interplay between nucleosomal transitions into states with crossed and ope...

Nano Letters, 2015

The bottom-up fabrication of ordered and oriented colloidal nanoparticle assemblies is critical f... more The bottom-up fabrication of ordered and oriented colloidal nanoparticle assemblies is critical for engineering functional nanomaterials beyond conventional polymer-particle composites. Here, we probe the influence of polymer surface ligands on the self-orientation of shaped metal nanoparticles for the formation of nanojunctions. We examine how polymer graft-surface interactions dictate Ag nanocube orientation into either edge-edge or face-face nanojunctions. Specifically, we investigate the effect of end-functionalized polymer grafts on nanocube assembly outcomes, such as interparticle angle and interparticle distance. Our assembly results can be directly mapped onto our theoretical phase diagrams for nanocube orientation, enabling correlation of experimental variables (such as graft length and metal binding strength) with computational parameters. These results represent an important step toward unifying modeling and experimental approaches to understanding nanoparticle-polymer self-assembly.

Macromolecules, 2015

ABSTRACT To provide insights into how polymer-grafted nanoparticles (NPs) enhance the viscoelasti... more ABSTRACT To provide insights into how polymer-grafted nanoparticles (NPs) enhance the viscoelastic properties of polymers, we have computed the frequency-dependent storage and loss modulus of coarse-grained models of polymer nanocomposites by means of molecular dynamics simulations. Nanocomposites containing NPs grafted with chains similar to those comprising the host polymer matrix exhibit considerably higher moduli than nanocomposites containing bare NPs across the entire frequency range investigated. This effect is shown to arise from the additional distortion of the shear field in the polymer matrix resulting from the grafted chains and from the slower relaxation time of the grafted chains compared to the matrix chains when the former are at least half as long as the latter. Increasing the attraction between the grafted and matrix chains results in further enhancement in the two moduli, but only at frequencies slower than those corresponding to the longest relaxation time of the chains. This effect is shown to arise from a dramatic slowdown in the relaxation dynamics of both the matrix and grafted chains. In addition, the nanocomposite moduli are found to increase with decreasing NP size and increasing NP loading, grafted chain length, and grafting density with varying frequency dependence. These parametric effects are also explained in terms of shear distortion effects and chain relaxation times. Based on these results, a phenomenological model is proposed to estimate the storage and loss modulus of such nanocomposites as a function of the Rouse relaxation times of the grafted and matrix chains and the volume fractions of the NPs, grafted chains, and matrix chains. The model captures the observed dependence of the moduli with the examined parameters of the grafted NPs and yields moduli predictions that agree quantitatively with those computed from the simulations at low frequencies.

Volume 8: Mechanics of Solids, Structures and Fluids, 2012

ABSTRACT The basis of this research is to mitigate shock through material design. In this work, w... more ABSTRACT The basis of this research is to mitigate shock through material design. In this work, we seek to develop an understanding of parametric variations in polyurea-based nano-composite materials through experimental characterization and computational modeling. Blast-mitigating applications often utilize polyurea due to its excellent thermo-mechanical properties. Polyurea is a microphase-separated segmented block copolymer formed by the rapid reaction of an isocyanate component and an amine component. Block copolymers exhibit unique properties as a result of their phase-separated morphology, which restricts dissimilar block components to microscopic length scales. The soft segments form a continuous matrix reinforced by the hard segments that are randomly dispersed as microdomains. The physical properties of the separate phases influence the overall properties of the polyurea. While polyurea offers a useful starting point, control over crystallite size and morphology is limited. For compositing, the blending approach allows superb control of particle size, shape, and density; however, the hard/soft interface is typically weak for simple blends. Here, we overcome this issue by developing hybrid polymer grafted nanoparticles, which have adjustable exposed functionality to control both their spatial distribution and interface. These nano-particles have tethered polymer chains that can interact with their surrounding environment and provide a method to control well defined and enhanced nano-composites. This approach allows us to adjust a number of variables related to the hybrid polymer grafted nanoparticles including: core size and shape, core material, polymer chain length, polymer chain density, and monomer type. In this work, we embark on a parametric study focusing on the effect of silica nanoparticle size, polymer chain length, and polymer chain density. Preliminary results from experimental characterization and computational modeling indicate that the dynamic mechanical properties of the material can be significantly altered through such parametric modifications. These efforts are part of an ongoing initiative to develop elastomeric composites with optimally designed compositions and characteristics to manage blast-induced stress-wave energy.

The Journal of Physical Chemistry A, 2009

To elucidate the role of the histone tails in chromatin compaction and in higher-order folding of... more To elucidate the role of the histone tails in chromatin compaction and in higher-order folding of chromatin under physiological conditions, we extend a mesoscale model of chromatin [Arya, Zhang, and Schlick, Biophys. J. 91, 133 (2006); Arya and Schlick, Proc. Natl. Acad. Sci. USA 103, 16236 (2006)] to account for divalent cations (Mg 2+ ) and linker histones. Configurations of 24-nucleosome oligonucleosomes in different salt environments and in the presence and absence of linker histones are sampled by a mixture of local and global Monte Carlo methods. Analyses of the resulting ensembles reveals a dynamic synergism between the histone tails, linker histones, and physiological ions in forming compact higher-order structures of chromatin. In the presence of monovalent salt alone, oligonucleosomes remain relatively unfolded and the histone tails do not mediate many internucleosomal interactions. Upon the addition of linker histones and divalent cations, the oligonucleosomes undergo a significant compaction triggered by: a dramatic increase in the internucleosomal interactions mediated by the histone tails; formation of a rigid linker DNA "stem" around the linker histones' C-terminal domains; and reducion in the electrostatic repulsion between linker DNAs via sharp bending in some linker DNAs caused by the divalent cations. Among all histone tails, the H4 tails mediate the most internucleosomal interactions, consistent with experimental observations, followed by the H3, H2A, and H2B tails in decreasing order. Apart from mediating internucleosomal interactions, the H3 tails also contribute to chromatin compaction by attaching to the entering and exiting linker DNA to screen electrotatic repulsion among the linker DNAs. This tendency of the H3 tails to attach to linker DNA, however, decreases significantly upon the addition of linker histones due to competition effects. The H2A and H2B tails do not mediate significant internucleosomal interactions but are important for mediating fiber/fiber intractions, especially in relatively unfolded chromatin in monovalent salt environments.

The Journal of Physical Chemistry B, 2001

The importance of pore exit effects on the diffusion of molecules in AlPO 4 -5 pores is evaluated... more The importance of pore exit effects on the diffusion of molecules in AlPO 4 -5 pores is evaluated using two molecular modeling techniques. In the first approach, a dual control volume grand canonical molecular dynamics technique is used to obtain molecular fluxes of methane out of the truncated crystal as a function of temperature and sorbate loading. The simulation results indicate the presence of a low-temperature surface barrier for diffusion, which retards the flux of methane relative to its apparent flux in the intracrystalline regions of the material. This pore exit barrier tends to diminish as temperature and loading increase. An explanation based on clustering phenomena is proposed to explain the latter. Next, a simple activated transport model is proposed to predict the relative importance of the surface barrier on the transport of sorbates in AlPO 4 -5. The potential of mean force for a single sorbate molecule along the pore axis of a truncated crystal provides the required activation energy barriers for the model. The model correctly predicts the reduction in the importance of exit effects with an increase in the temperature. It is also observed that exit effects become more important as the ratio of the size of the sorbate molecule to the pore size approaches unity. In particular, exit effects are significant in micrometer-thick AlPO 4 -5 crystals in the case of large molecules such as SnBr 4 and CCl 4 at room temperature.

Chemical Physics, 2000

A new momentum impulse relaxation method for obtaining the shear viscosity of Newtonian fluids us... more A new momentum impulse relaxation method for obtaining the shear viscosity of Newtonian fluids using molecular dynamics simulations is introduced. The method involves the resolution of a decaying coarse-grain Gaussian velocity profile in a properly thermostated simulation box. This localized velocity profile, along with a modification of the periodic boundary conditions, allows computations in a periodic box with minimal phonon

Chemical Physics, 2001

Transport in an idealized model with variable pore diameter as well as an AlPO4-5 zeolite is exam... more Transport in an idealized model with variable pore diameter as well as an AlPO4-5 zeolite is examined using three different molecular dynamics techniques: (1) equilibrium molecular dynamics (EMD); (2) external field nonequilibrium molecular dynamics (EF-NEMD) and (3) dual control volume grand canonical molecular dynamics (DCV-GCMD). The EMD and EF-NEMD methods yield identical transport coefficients for all the systems studied. The

The Journal of Physical Chemistry B, 2009

The energetic and entropic interactions governing the attraction between like-charged colloidal p... more The energetic and entropic interactions governing the attraction between like-charged colloidal particles grafted with oppositely charged polyelectrolyte chains in a monovalent electrolyte are investigated computationally. We employ coarse-grained models of the colloids with varying surface and polyelectrolyte charges and Monte Carlo simulations to compute the potential of mean force between two colloidal particles as a function of their separation distance. By categorizing the potentials as attractive or purely repulsive, we obtain the extent and location of the attractive-force regime within the two-dimensional parameter space comprised of the colloid surface and polyelectrolyte charge. The attractive regime is found to occupy the inside of a hyperbola in this charge space, whose shape and size is determined by a complex interplay between energetic and entropic interactions. In particular, we find that the strength of attraction at short distances is governed by a balance between favorable energetic and entropic terms arising from polymer-bridging interactions, unfavorable energies arising from the mutual repulsion of the colloid surfaces and polyelectrolyte chains, and unfavorable entropies arising from the overlap and crowding effects of chains confined between the colloid surfaces. A phenomenological model is proposed to explain the hyperbolic shape of the attractive regime and make useful predictions about changes in its shape and location for conditions not investigated in this study.

Proceedings of the National Academy of Sciences, 2006

The role of each histone tail in regulating chromatin structure is elucidated by using a coarse-g... more The role of each histone tail in regulating chromatin structure is elucidated by using a coarse-grained model of an oligonucleosome incorporating flexible histone tails that reproduces the conformational and dynamical properties of chromatin. Specifically, a tailored configurational-bias Monte Carlo method that efficiently samples the possible conformational states of oligonucleosomes yields positional distributions of histone tails around nucleosomes and illuminates the nature of tail͞core͞DNA interactions at various salt milieus. Analyses indicate that the H4 histone tails are most important in terms of mediating internucleosomal interactions, especially in highly compact chromatin with linker histones, followed by H3, H2A, and H2B tails in decreasing order of importance. In addition to mediating internucleosomal interactions, the H3 histone tails crucially screen the electrostatic repulsion between the entering͞exiting DNA linkers. The H2A and H2B tails distribute themselves along the periphery of chromatin fibers and are important for mediating fiber͞fiber interactions. A delicate balance between tail-mediated internucleosomal attraction and repulsion among linker DNAs allows the entering͞exiting linker DNAs to align perpendicular to each other in linker-histone deficient chromatin, leading to the formation of an irregular zigzag-folded fiber with dominant pair-wise interactions between nucleosomes i and i ؎ 4.

Physical Review Letters, 2010

Single-molecule force spectroscopy provides a powerful approach for investigating molecular trans... more Single-molecule force spectroscopy provides a powerful approach for investigating molecular transitions along specific reaction coordinates. Here, we present a general analytical model for extracting the intrinsic rates and activation free energies from force measurements on single molecules that is applicable to a broad range of pulling speeds and device stiffnesses. This model relaxes existing limitations to perform force measurements with soft pulling devices for proper theoretical analyses and, in fact, allows experiments to specifically exploit device stiffness as a control parameter in addition to pulling speed for a reliable estimation of energetic and kinetic parameters.

Physical Review Letters, 2003

An analytic theory for the Knudsen self-diffusivity D s of hard spheres in an atomically rough sl... more An analytic theory for the Knudsen self-diffusivity D s of hard spheres in an atomically rough slitshaped pore is presented which quantitatively matches simulation results. The theory assumes that, due to chaotic molecular trajectories caused by surface morphology, collisions of gas molecules with the wall are partly diffuse and partly specular, the relative magnitude of each depending upon the magnitude of the tangential momentum accommodation coefficient f. The theory thus represents a universal Knudsen fluctuation-dissipation correlation between longitudinal momentum loss and diffusivity that can simplify efforts to estimate D s . It is also found that D s computed using Maxwell's theory of slip, in which collisions with the walls are assumed to be purely diffuse or specular, overpredicts the simulated D s by a large margin.