Modeling of solvent flow effects in enzyme catalysis under physiological conditions

A stochastic model for the dynamics of enzymatic catalysis in explicit, effective solvents under physiological conditions is presented. Analytically-computed first passage time densities of a diffusing particle in a spherical shell with absorbing boundaries are combined with densities obtained from explicit simulation to obtain the overall probability density for the total reaction cycle time of the enzymatic system. The method is used to investigate the catalytic transfer of a phosphoryl group in a phosphoglycerate kinase-ADP-bis phosphoglycerate system, one of the steps of glycolysis. The direct simulation of the enzyme-substrate binding and reaction is carried out using an elastic network model for the protein, and the solvent motions are described by multiparticle collision dynamics, which incorporates hydrodynamic flow effects. Systems where solvent-enzyme coupling occurs through explicit intermolecular interactions, as well as systems where this coupling is taken into account by including the protein and substrate in the multiparticle collision step, are investigated and compared with simulations where hydrodynamic coupling is absent. It is demonstrated that the flow of solvent particles around the enzyme facilitates the large-scale hinge motion of the enzyme with bound substrates, and has a significant impact on the shape of the probability densities and average time scales of substrate binding for substrates near the enzyme, the closure of the enzyme after binding, and the overall time of completion of the cycle.Comment: 15 pages in double column forma

The statistics of particle velocities in dense granular flows

We present measurements of the particle velocity distribution in the flow of granular material through vertical channels. Our study is confined to dense, slow flows where the material shears like a fluid only in thin layers adjacent to the walls, while a large core moves without continuous deformation, like a solid. We find the velocity distribution to be non-Gaussian, anisotropic, and to follow a power law at large velocities. Remarkably, the distribution is identical in the fluid-like and solid-like regions. The velocity variance is maximum at the core, defying predictions of hydrodynamic theories. We show evidence of spatially correlated motion, and propose a mechanism for the generation of fluctuational motion in the absence of shear.Comment: Submitted to Phys. Rev. Let

Breakdown of weak-field magnetotransport at a metallic quantum critical point

We show how the collapse of an energy scale in a quantum critical metal can lead to physics beyond the weak-field limit usually used to compute transport quantities. For a density-wave transition we show that the presence of a finite magnetic field at the critical point leads to discontinuities in the transport coefficients as temperature tends to zero. The origin of these discontinuities lies in the breakdown of the weak field Jones-Zener expansion which has previously been used to argue that magneto-transport coefficients are continuous at simple quantum critical points. The presence of potential scattering and magnetic breakdown rounds the discontinuities over a window determined by tau Delta < 1 where Delta is the order parameter and tau is the quasiparticle elastic lifetime.Comment: 4 pages, 3 figures RevTeX forma

Multiple-Point and Multiple-Time Correlations Functions in a Hard-Sphere Fluid

A recent mode coupling theory of higher-order correlation functions is tested on a simple hard-sphere fluid system at intermediate densities. Multi-point and multi-time correlation functions of the densities of conserved variables are calculated in the hydrodynamic limit and compared to results obtained from event-based molecular dynamics simulations. It is demonstrated that the mode coupling theory results are in excellent agreement with the simulation results provided that dissipative couplings are included in the vertices appearing in the theory. In contrast, simplified mode coupling theories in which the densities obey Gaussian statistics neglect important contributions to both the multi-point and multi-time correlation functions on all time scales.Comment: Second one in a sequence of two (in the first, the formalism was developed). 12 pages REVTeX. 5 figures (eps). Submitted to Phys.Rev.

Mode-coupling theory for multiple-time correlation functions of tagged particle densities and dynamical filters designed for glassy systems

The theoretical framework for higher-order correlation functions involving multiple times and multiple points in a classical, many-body system developed by Van Zon and Schofield [Phys. Rev. E 65, 011106 (2002)] is extended here to include tagged particle densities. Such densities have found an intriguing application as proposed measures of dynamical heterogeneities in structural glasses. The theoretical formalism is based upon projection operator techniques which are used to isolate the slow time evolution of dynamical variables by expanding the slowly-evolving component of arbitrary variables in an infinite basis composed of the products of slow variables of the system. The resulting formally exact mode-coupling expressions for multiple-point and multiple-time correlation functions are made tractable by applying the so-called N-ordering method. This theory is used to derive for moderate densities the leading mode coupling expressions for indicators of relaxation type and domain relaxation, which use dynamical filters that lead to multiple-time correlations of a tagged particle density. The mode coupling expressions for higher order correlation functions are also succesfully tested against simulations of a hard sphere fluid at relatively low density.Comment: 15 pages, 2 figure

Drying of complex suspensions

We investigate the 3D structure and drying dynamics of complex mixtures of emulsion droplets and colloidal particles, using confocal microscopy. Air invades and rapidly collapses large emulsion droplets, forcing their contents into the surrounding porous particle pack at a rate proportional to the square of the droplet radius. By contrast, small droplets do not collapse, but remain intact and are merely deformed. A simple model coupling the Laplace pressure to Darcy's law correctly estimates both the threshold radius separating these two behaviors, and the rate of large-droplet evacuation. Finally, we use these systems to make novel hierarchical structures.Comment: 4 pages, 4 figure

Mutation analysis of HIF prolyl hydroxylases (PHD/EGLN) in individuals with features of phaeochromocytoma and renal cell carcinoma susceptibility

Germline mutations in the von Hippel–Lindau disease (VHL) and succinate dehydrogenase subunit B (SDHB) genes can cause inherited phaeochromocytoma and/or renal cell carcinoma(RCC). Dysregulation of the hypoxia-inducible factor (HIF) transcription factors has been linked to VHL and SDHB-related RCC; both HIF dysregulation and disordered function of a prolyl hydroxylase domain isoform 3 (PHD3/EGLN3)-related pathway of neuronal apoptosis have been linked to the development of phaeochromocytoma. The 2-oxoglutarate-dependent prolyl hydroxylase enzymes PHD1 (EGLN2), PHD2 (EGLN1) and PHD3 (EGLN3) have a key role in regulating the stability of HIF-a subunits (and hence expression of the HIF-a transcription factors). A germline PHD2 mutation has been reported in association with congenital erythrocytosis and recurrent extra-adrenal phaeochromocytoma. We undertook mutation analysis of PHD1, PHD2 and PHD3 in two cohorts of patients with features of inherited phaeochromocytoma (nZ82) and inherited RCC (nZ64) and no evidence of germline mutations in known susceptibility genes. No confirmed pathogenic mutations were detected suggesting that mutations in these genes are not a frequent cause of inherited phaeochromocytoma or RCC

Quantum free energy differences from non-equilibrium path integrals: I. Methods and numerical application

The imaginary-time path integral representation of the canonical partition function of a quantum system and non-equilibrium work fluctuation relations are combined to yield methods for computing free energy differences in quantum systems using non-equilibrium processes. The path integral representation is isomorphic to the configurational partition function of a classical field theory, to which a natural but fictitious Hamiltonian dynamics is associated. It is shown that if this system is prepared in an equilibrium state, after which a control parameter in the fictitious Hamiltonian is changed in a finite time, then formally the Jarzynski non-equilibrium work relation and the Crooks fluctuation relation are shown to hold, where work is defined as the change in the energy as given by the fictitious Hamiltonian. Since the energy diverges for the classical field theory in canonical equilibrium, two regularization methods are introduced which limit the number of degrees of freedom to be finite. The numerical applicability of the methods is demonstrated for a quartic double-well potential with varying asymmetry. A general parameter-free smoothing procedure for the work distribution functions is useful in this context.Comment: 20 pages, 4 figures. Added clarifying remarks and fixed typo

Self-consistent Overhauser model for the pair distribution function of an electron gas at finite temperature

We present calculations of the spin-averaged pair distribution function $g(r)$ in a homogeneous gas of electrons moving in dimensionality D=3 or D=2 at finite temperature. The model involves the solution of a two-electron scattering problem via an effective potential which embodies many-body effects through a self-consistent Hartree approximation, leading to two-body wave functions to be averaged over a temperature-dependent distribution of relative momentum for electron pairs. We report illustrative numerical results for $g(r)$ in an intermediate-coupling regime and interpret them in terms of changes of short-range order with increasing temperature.Comment: 6 pages, 5 figures, submitted to Solid State Communication

Thermal tides in the Martian middle atmosphere as seen by the Mars Climate Sounder

The first systematic observations of the middle atmosphere of Mars (35–80km) with the Mars Climate Sounder (MCS) show dramatic patterns of diurnal thermal variation, evident in retrievals of temperature and water ice opacity. At the time of writing, the data set of MCS limb retrievals is sufficient for spectral analysis within a limited range of latitudes and seasons. This analysis shows that these thermal variations are almost exclusively associated with a diurnal thermal tide. Using a Martian general circulation model to extend our analysis, we show that the diurnal thermal tide dominates these patterns for all latitudes and all seasons