Benchmarking pKa prediction

Background: pKa values are a measure of the protonation of ionizable groups in proteins. Ionizable groups are involved in intra-protein, protein-solvent and protein-ligand interactions as well as solubility, protein folding and catalytic activity. The pKa shift of a group from its intrinsic value is determined by the perturbation of the residue by the environment and can be calculated from three-dimensional structural data. Results: Here we use a large dataset of experimentally-determined pKas to analyse the performance of different prediction techniques. Our work provides a benchmark of available software implementations: MCCE, MEAD, PROPKA and UHBD. Combinatorial and regression analysis is also used in an attempt to find a consensus approach towards pKa prediction. The tendency of individual programs to over- or underpredict the pKa value is related to the underlying methodology of the individual programs. Conclusion: Overall, PROPKA is more accurate than the other three programs. Key to developing accurate predictive software will be a complete sampling of conformations accessible to protein structures

Localized Flux Lines and the Bose Glass

Columnar defects provide effective pinning centers for magnetic flux lines in high--$T_{\rm c}$ superconductors. Utilizing a mapping of the statistical mechanics of directed lines to the quantum mechanics of two--dimensional bosons, one expects an entangled flux liquid phase at high temperatures, separated by a second--order localization transition from a low--temperature ``Bose glass'' phase with infinite tilt modulus. Recent decoration experiments have demonstrated that below the matching field the repulsive forces between the vortices may be sufficiently large to produce strong spatial correlations in the Bose glass. This is confirmed by numerical simulations, and a remarkably wide soft ``Coulomb gap'' at the chemical potential is found in the distribution of pinning energies. At low currents, the dominant transport mechanism in the Bose glass phase proceeds via the formation of double kinks between not necessarily adjacent columnar pins, similar to variable--range hopping in disordered semiconductors. The strong correlation effects originating in the long--range vortex interactions drastically reduce variable--range hopping transport.Comment: 10 pages, latex ("lamuphys.sty" file included), 6 figures can be obtained from the author ([email protected]); to appear in Proc. XIV Sitges conference on "Complex Behaviour of Glassy Systems" (Springer--Verlag

Statistical deconvolution of enthalpic energetic contributions to MHC-peptide binding affinity

Background: MHC Class I molecules present antigenic peptides to cytotoxic T cells, which forms an integral part of the adaptive immune response. Peptides are bound within a groove formed by the MHC heavy chain. Previous approaches to MHC Class I-peptide binding prediction have largely concentrated on the peptide anchor residues located at the P2 and C-terminus positions. Results: A large dataset comprising MHC-peptide structural complexes was created by re-modelling pre-determined x-ray crystallographic structures. Static energetic analysis, following energy minimisation, was performed on the dataset in order to characterise interactions between bound peptides and the MHC Class I molecule, partitioning the interactions within the groove into van der Waals, electrostatic and total non-bonded energy contributions. Conclusion: The QSAR techniques of Genetic Function Approximation (GFA) and Genetic Partial Least Squares (G/PLS) algorithms were used to identify key interactions between the two molecules by comparing the calculated energy values with experimentally-determined BL50 data. Although the peptide termini binding interactions help ensure the stability of the MHC Class I-peptide complex, the central region of the peptide is also important in defining the specificity of the interaction. As thermodynamic studies indicate that peptide association and dissociation may be driven entropically, it may be necessary to incorporate entropic contributions into future calculations

Properties of the Bose glass phase in irradiated superconductors near the matching field

Structural and transport properties of interacting localized flux lines in the Bose glass phase of irradiated superconductors are studied by means of Monte Carlo simulations near the matching field B_Phi, where the densities of vortices and columnar defects are equal. For a completely random columnar pin distribution in the xy-plane transverse to the magnetic field, our results show that the repulsive vortex interactions destroy the Mott insulator phase which was predicted to occur at B = B_Phi. On the other hand, for ratios of the penetration depth to average defect distance lambda/d <= 1, characteristic remnants of the Mott insulator singularities remain visible in experimentally accessible quantities as the magnetization, the bulk modulus, and the magnetization relaxation, when B is varied near B_Phi. For spatially more regular disorder, e.g., a nearly triangular defect distribution, we find that the Mott insulator phase can survive up to considerably large interaction range \lambda/d, and may thus be observable in experiments.Comment: RevTex, 17 pages, eps files for 12 figures include

Interactions, Distribution of Pinning Energies, and Transport in the Bose Glass Phase of Vortices in Superconductors

We study the ground state and low energy excitations of vortices pinned to columnar defects in superconductors, taking into account the long--range interaction between the fluxons. We consider the ``underfilled'' situation in the Bose glass phase, where each flux line is attached to one of the defects, while some pins remain unoccupied. By exploiting an analogy with disordered semiconductors, we calculate the spatial configurations in the ground state, as well as the distribution of pinning energies, using a zero--temperature Monte Carlo algorithm minimizing the total energy with respect to all possible one--vortex transfers. Intervortex repulsion leads to strong correlations whenever the London penetration depth exceeds the fluxon spacing. A pronounced peak appears in the static structure factor $S(q)$ for low filling fractions $f \leq 0.3$. Interactions lead to a broad Coulomb gap in the distribution of pinning energies $g(\epsilon)$ near the chemical potential $\mu$, separating the occupied and empty pins. The vanishing of $g(\epsilon)$ at $\mu$ leads to a considerable reduction of variable--range hopping vortex transport by correlated flux line pinning.Comment: 16 pages (twocolumn), revtex, 16 figures not appended, please contact [email protected]

Sticky stuff : redefining bedform prediction in modern and ancient environments

This work was funded by the UK Natural Environment Research Council (NERC) under the COHBED project (NE/1027223/1). Paterson was funded by the Marine Alliance for Science and Technology for Scotland (MASTS).The dimensions and dynamics of subaqueous bedforms are well known for cohesionless sediments. However, the effect of physical cohesion imparted by cohesive clay within mixed sand-mud substrates has not been examined, despite its recognized influence on sediment stability. Here we present a series of controlled laboratory experiments to establish the influence of substrate clay content on subaqueous bedform dynamics within mixtures of sand and clay exposed to unidirectional flow. The results show that bedform dimensions and steepness decrease linearly with clay content, and comparison with existing predictors of bedform dimensions, established within cohesionless sediments, reveals significant over-prediction of bedform size for all but the lowermost clay contents examined. The profound effect substrate clay content has on bedform dimensions has a number of important implications for interpretation in a range of modern and ancient environments, including reduced roughness and bedform heights in estuarine systems and the often cited lack of large dune cross-sets in turbidites. The results therefore offer a step change in our understanding of bedform formation and dynamics in these, and many other, sedimentary environments.Publisher PDFPeer reviewe

Simulations of neutron background in a time projection chamber relevant to dark matter searches

Presented here are results of simulations of neutron background performed for a time projection chamber acting as a particle dark matter detector in an underground laboratory. The investigated background includes neutrons from rock and detector components, generated via spontaneous fission and (alpha, n) reactions, as well as those due to cosmic-ray muons. Neutrons were propagated to the sensitive volume of the detector and the nuclear recoil spectra were calculated. Methods of neutron background suppression were also examined and limitations to the sensitivity of a gaseous dark matter detector are discussed. Results indicate that neutrons should not limit sensitivity to WIMP-nucleon interactions down to a level of (1 - 3) x 10^{-8} pb in a 10 kg detector.Comment: 27 pages (total, including 3 tables and 11 figures). Accepted for publication in Nuclear Instruments and Methods in Physics Research - Section

Familial influences on sustained attention and inhibition in preschoolers

Background: In this study several aspects of attention were studied in 237 nearly 6-year-old twin pairs. Specifically, the ability to sustain attention and inhibition were investigated using a computerized test battery (Amsterdam Neuropsychological Tasks). Furthermore, the Teacher's Report Form (TRF) was filled out by the teacher of the child and the attention subscale of this questionnaire was analyzed. Methods: The variance in performance on the different tasks of the test battery and the score on the attention scale of the TRF were decomposed into a contribution of the additive effects of many genes (A), environmental effects that are shared by twins (C) and unique environmental influences not shared by twins (E) by using data from MZ and DZ twins. Results: The genetic model fitting results showed an effect of A and E for the attention scale of the TRF, and for some of the inhibition and sustained attention measures. For most of the attention variables, however, it was not possible to decide between a model with A and E or a model with C and E. Time-on-task effects on reaction time or number of errors and the delay after making an error did not show familial resemblances. A remarkable finding was that the heritability of the attention scale of the TRF was found to be higher than the heritability of indices that can be considered to be more direct measures of attention, such as mean tempo in the sustained attention task and response speed in the Go-NoGo task. Conclusion: In preschoolers, familial resemblances on sustained attention and inhibition were observed. © Association for Child Psychology and Psychiatry, 2004

Neutron background in large-scale xenon detectors for dark matter searches

Simulations of the neutron background for future large-scale particle dark matter detectors are presented. Neutrons were generated in rock and detector elements via spontaneous fission and (alpha,n) reactions, and by cosmic-ray muons. The simulation techniques and results are discussed in the context of the expected sensitivity of a generic liquid xenon dark matter detector. Methods of neutron background suppression are investigated. A sensitivity of $10^{-9}-10^{-10}$ pb to WIMP-nucleon interactions can be achieved by a tonne-scale detector.Comment: 35 pages, 13 figures, 2 tables, accepted for publication in Astroparticle Physic

Binding Energy of Charged Excitons in ZnSe-based Quantum Wells

Excitons and charged excitons (trions) are investigated in ZnSe-based quantum well structures with (Zn,Be,Mg)Se and (Zn,Mg)(S,Se) barriers by means of magneto-optical spectroscopy. Binding energies of negatively () and positively (X+) charged excitons are measured as functions of quantum well width, free carrier density and in external magnetic fields up to 47 T. The binding energy of shows a strong increase from 1.4 to 8.9 meV with decreasing quantum well width from 190 to 29 A. The binding energies of X+ are about 25% smaller than the binding energy in the same structures. The magnetic field behavior of and X+ binding energies differ qualitatively. With growing magnetic field strength, increases its binding energy by 35-150%, while for X+ it decreases by 25%. Zeeman spin splittings and oscillator strengths of excitons and trions are measured and discussed