Simulating rare events using a Weighted Ensemble-based string method

We introduce an extension to the Weighted Ensemble (WE) path sampling method to restrict sampling to a one dimensional path through a high dimensional phase space. Our method, which is based on the finite-temperature string method, permits efficient sampling of both equilibrium and non-equilibrium systems. Sampling obtained from the WE method guides the adaptive refinement of a Voronoi tessellation of order parameter space, whose generating points, upon convergence, coincide with the principle reaction pathway. We demonstrate the application of this method to several simple, two-dimensional models of driven Brownian motion and to the conformational change of the nitrogen regulatory protein C receiver domain using an elastic network model. The simplicity of the two-dimensional models allows us to directly compare the efficiency of the WE method to conventional brute force simulations and other path sampling algorithms, while the example of protein conformational change demonstrates how the method can be used to efficiently study transitions in the space of many collective variables

Simulations of the Alternating Access Mechanism of the Sodium Symporter Mhp1

AbstractSodium coupled cotransporters of the five-helix inverted repeat (5HIR) superfamily use an alternating access mechanism to transport a myriad of small molecules across the cell membrane. One of the primary steps in this mechanism is the conformational transition from a state poised to bind extracellular substrates to a state that is competent to deliver substrate to the cytoplasm. Here, we construct a coarse-grained model of the 5HIR benzylhydantoin transporter Mhp1 that incorporates experimental structures of the outward- and inward-open states to investigate the mechanism of this conformational change. Using the weighted ensemble path-sampling method, we rigorously sample the outward- to inward-facing transition path ensemble. The transition path ensemble reveals a heterogeneous set of pathways connecting the two states and identifies two modes of transport: one consistent with a strict alternating access mechanism and another where decoupling of the inner and outer gates causes the transient formation of a continuous permeation pathway through the transporter. We also show that the conformational switch between the outward- and inward-open states results from rigid body motions of the hash motif relative to the substrate bundle, supporting the rocking bundle hypothesis. Finally, our methodology provides the groundwork for more chemically detailed investigations of the alternating mechanism

Stochastic steps in secondary active sugar transport.

Secondary active transporters, such as those that adopt the leucine-transporter fold, are found in all domains of life, and they have the unique capability of harnessing the energy stored in ion gradients to accumulate small molecules essential for life as well as expel toxic and harmful compounds. How these proteins couple ion binding and transport to the concomitant flow of substrates is a fundamental structural and biophysical question that is beginning to be answered at the atomistic level with the advent of high-resolution structures of transporters in different structural states. Nonetheless, the dynamic character of the transporters, such as ion/substrate binding order and how binding triggers conformational change, is not revealed from static structures, yet it is critical to understanding their function. Here, we report a series of molecular simulations carried out on the sugar transporter vSGLT that lend insight into how substrate and ions are released from the inward-facing state of the transporter. Our simulations reveal that the order of release is stochastic. Functional experiments were designed to test this prediction on the human homolog, hSGLT1, and we also found that cytoplasmic release is not ordered, but we confirmed that substrate and ion binding from the extracellular space is ordered. Our findings unify conflicting published results concerning cytoplasmic release of ions and substrate and hint at the possibility that other transporters in the superfamily may lack coordination between ions and substrate in the inward-facing state

Discovery of A Very Bright, Strongly-Lensed z=2 Galaxy in the SDSS DR5

We report on the discovery of a very bright z = 2.00 star-forming galaxy that is strongly lensed by a foreground z=0.422 luminous red galaxy (LRG). This system was found in a systematic search for bright arcs lensed by LRGs and brightest cluster galaxies in the Sloan Digital Sky Survey Data Release 5 sample. Follow-up observations on the Subaru 8.2m telescope on Mauna Kea and the Astrophysical Research Consortium 3.5m telescope at Apache Point Observatory confirmed the lensing nature of this system. A simple lens model for the system, assuming a singular isothermal ellipsoid mass distribution, yields an Einstein radius of 3.82 +/- 0.03 arcsec or 14.8 +/- 0.1 kpc/h at the lens redshift. The total projected mass enclosed within the Einstein radius is 2.10 +/- 0.03 x 10^12 M_sun/h, and the magnification factor for the source galaxy is 27 +/- 1. Combining the lens model with our gVriz photometry, we find an (unlensed) star formation rate for the source galaxy of 32 M_sun/h / yr, adopting a fiducial constant star formation rate model with an age of 100 Myr and E(B-V) = 0.25. With an apparent magnitude of r = 19.9, this system is among the very brightest lensed z >= 2 galaxies, and provides an excellent opportunity to pursue detailed studies of the physical properties of an individual high-redshift star-forming galaxy.Comment: 31 pages, 12 figures, 4 tables, submitted to Ap

The Mechanical Properties of PCNA: Implications for the Loading and Function of a DNA Sliding Clamp

Sliding clamps are toroidal proteins that encircle DNA and act as mobile platforms for DNA replication and repair machinery. To be loaded onto DNA, the eukaryotic sliding clamp Proliferating Cell Nuclear Antigen (PCNA) must be splayed open at one of the subunit-subunit interfaces by the ATP-dependent clamp loader, Replication Factor C, whose clamp-interacting sites form a right-handed spiral. Earlier molecular dynamics (MD) studies suggested that when PCNA opens, it preferentially adopts a right-handed spiral to match the spiral of the clamp loader. Here, analysis of considerably longer MD simulations shows that although the opened form of PCNA can achieve conformations matching the helical pitch of Replication Factor C, it is not biased toward a right-handed spiral structure. A coarse-grained elastic model was also built; its strong correspondence to the all-atom MD simulations of PCNA suggests that the behavior of the open clamp is primarily due to elastic deformation governed by the topology of the clamp domains. The elastic model was further used to construct the energy landscape of the opened PCNA clamp, including conformations that would allow binding to the clamp loader and loading onto double-stranded DNA. A picture of PCNA emerges of a rather flexible protein that, once opened, is mechanically compliant in the clamp opening process

The Sloan Digital Sky Survey Quasar Lens Search. VI. Constraints on Dark Energy and the Evolution of Massive Galaxies

We present a statistical analysis of the final lens sample from the Sloan Digital Sky Survey Quasar Lens Search (SQLS). The number distribution of a complete subsample of 19 lensed quasars selected from 50,836 source quasars is compared with theoretical expectations, with particular attention to the selection function. Assuming that the velocity function of galaxies does not evolve with redshift, the SQLS sample constrains the cosmological constant to \Omega_\Lambda=0.79^{+0.06}_{-0.07}(stat.)^{+0.06}_{-0.06}(syst.) for a flat universe. The dark energy equation of state is found to be consistent with w=-1 when the SQLS is combined with constraints from baryon acoustic oscillation (BAO) measurements or results from the Wilkinson Microwave Anisotropy Probe (WMAP). We also obtain simultaneous constraints on cosmological parameters and redshift evolution of the galaxy velocity function, finding no evidence for redshift evolution at z<1 in any combinations of constraints. For instance, number density evolution quantified as \nu_n=d\ln\phi_*/d\ln(1+z) and the velocity dispersion evolution \nu_\sigma=d\ln\sigma_*/d\ln(1+z) are constrained to \nu_n=1.06^{+1.36}_{-1.39}(stat.)^{+0.33}_{-0.64}(syst.) and \nu_\sigma=-0.05^{+0.19}_{-0.16}(stat.)^{+0.03}_{-0.03}(syst.) respectively when the SQLS result is combined with BAO and WMAP for flat models with a cosmological constant. We find that a significant amount of dark energy is preferred even after fully marginalizing over the galaxy evolution parameters. Thus the statistics of lensed quasars robustly confirm the accelerated cosmic expansion.Comment: 44 pages, 12 figures, 4 tables, accepted for publication in A

The Sloan Digital Sky Survey Quasar Lens Search. V. Final Catalog from the Seventh Data Release

We present the final statistical sample of lensed quasars from the Sloan Digital Sky Survey (SDSS) Quasar Lens Search (SQLS). The well-defined statistical lens sample consists of 26 lensed quasars brighter than i=19.1 and in the redshift range of 0.6<z<2.2 selected from 50,836 spectroscopically confirmed quasars in the SDSS Data Release 7 (DR7), where we restrict the image separation range to 1"<\theta<20" and the i-band magnitude differences in two image lenses to be smaller than 1.25 mag. The SDSS DR7 quasar catalog also contains 36 additional lenses identified with various techniques. In addition to these lensed quasars, we have identified 81 pairs of quasars from follow-up spectroscopy, 26 of which are physically associated binary quasars. The statistical lens sample covers a wide range of image separations, redshifts, and magnitudes, and therefore is suitable for systematic studies of cosmological parameters and surveys of the structure and evolution of galaxies and quasars.Comment: 42 pages, 2 figures, 6 tables, accepted for publication in AJ; see http://www-utap.phys.s.u-tokyo.ac.jp/~sdss/sqls/ for supplemental informatio

The Sloan Digital Sky Survey Quasar Lens Search. IV. Statistical Lens Sample from the Fifth Data Release

We present the second report of our systematic search for strongly lensed quasars from the data of the Sloan Digital Sky Survey (SDSS). From extensive follow-up observations of 136 candidate objects, we find 36 lenses in the full sample of 77,429 spectroscopically confirmed quasars in the SDSS Data Release 5. We then define a complete sample of 19 lenses, including 11 from our previous search in the SDSS Data Release 3, from the sample of 36,287 quasars with i<19.1 in the redshift range 0.6<z<2.2, where we require the lenses to have image separations of 1"<\theta<20" and i-band magnitude differences between the two images smaller than 1.25 mag. Among the 19 lensed quasars, 3 have quadruple-image configurations, while the remaining 16 show double images. This lens sample constrains the cosmological constant to be \Omega_\Lambda=0.84^{+0.06}_{-0.08}(stat.)^{+0.09}_{-0.07}(syst.) assuming a flat universe, which is in good agreement with other cosmological observations. We also report the discoveries of 7 binary quasars with separations ranging from 1.1" to 16.6", which are identified in the course of our lens survey. This study concludes the construction of our statistical lens sample in the full SDSS-I data set.Comment: 37 pages, 2 figures and 5 tables, accepted to A

The Sloan Digital Sky Survey-II Supernova Survey: Search Algorithm and Follow-up Observations

The Sloan Digital Sky Survey-II Supernova Survey has identified a large number of new transient sources in a 300 sq. deg. region along the celestial equator during its first two seasons of a three-season campaign. Multi-band (ugriz) light curves were measured for most of the sources, which include solar system objects, Galactic variable stars, active galactic nuclei, supernovae (SNe), and other astronomical transients. The imaging survey is augmented by an extensive spectroscopic follow-up program to identify SNe, measure their redshifts, and study the physical conditions of the explosions and their environment through spectroscopic diagnostics. During the survey, light curves are rapidly evaluated to provide an initial photometric type of the SNe, and a selected sample of sources are targeted for spectroscopic observations. In the first two seasons, 476 sources were selected for spectroscopic observations, of which 403 were identified as SNe. For the Type Ia SNe, the main driver for the Survey, our photometric typing and targeting efficiency is 90%. Only 6% of the photometric SN Ia candidates were spectroscopically classified as non-SN Ia instead, and the remaining 4% resulted in low signal-to-noise, unclassified spectra. This paper describes the search algorithm and the software, and the real-time processing of the SDSS imaging data. We also present the details of the supernova candidate selection procedures and strategies for follow-up spectroscopic and imaging observations of the discovered sources.Comment: Accepted for publication in The Astronomical Journal (66 pages, 13 figures); typos correcte

HETDEX pilot survey for emission-line galaxies - I. Survey design, performance, and catalog

We present a catalog of emission-line galaxies selected solely by their emission-line fluxes using a wide-field integral field spectrograph. This work is partially motivated as a pilot survey for the upcoming Hobby-Eberly Telescope Dark Energy Experiment (HETDEX). We describe the observations, reductions, detections, redshift classifications, line fluxes, and counterpart information for 397 emission-line galaxies detected over 169 sq.arcmin with a 3500-5800 Ang. bandpass under 5 Ang. full-width-half-maximum (FWHM) spectral resolution. The survey's best sensitivity for unresolved objects under photometric conditions is between 4-20 E-17 erg/s/sq.cm depending on the wavelength, and Ly-alpha luminosities between 3-6 E42 erg/s are detectable. This survey method complements narrowband and color-selection techniques in the search for high redshift galaxies with its different selection properties and large volume probed. The four survey fields within the COSMOS, GOODS-N, MUNICS, and XMM-LSS areas are rich with existing, complementary data. We find 104 galaxies via their high redshift Ly-alpha emission at 1.9<z<3.8, and the majority of the remainder objects are low redshift [OII]3727 emitters at z<0.56. The classification between low and high redshift objects depends on rest frame equivalent width, as well as other indicators, where available. Based on matches to X-ray catalogs, the active galactic nuclei (AGN) fraction amongst the Ly-alpha emitters (LAEs) is 6%. We also analyze the survey's completeness and contamination properties through simulations. We find five high-z, highly-significant, resolved objects with full-width-half-maximum sizes >44 sq.arcsec which appear to be extended Ly-alpha nebulae. We also find three high-z objects with rest frame Ly-alpha equivalent widths above the level believed to be achievable with normal star formation, EW(rest)>240 Ang.Comment: 45 pages, 36 figures, 5 tables, submitted to ApJ