Chirality and Protein Folding

There are several simple criteria of folding to a native state in model proteins. One of them involves crossing of a threshold value of the RMSD distance away from the native state. Another checks whether all native contacts are established, i.e. whether the interacting amino acids come closer than some characteristic distance. We use Go-like models of proteins and show that such simple criteria may prompt one to declare folding even though fragments of the resulting conformations have a wrong sense of chirality. We propose that a better condition of folding should augment the simple criteria with the requirement that most of the local values of the chirality should be nearly native. The kinetic discrepancy between the simple and compound criteria can be substantially reduced in the Go-like models by providing the Hamiltonian with a term which favors native values of the local chirality. We study the effects of this term as a function of its amplitude and compare it to other models such as with the side groups and with the angle-dependent potentials.Comment: To be published in a special issue of J. Phys.: Cond. Mat. (Bedlewo Workshop

Effects of confinement and crowding on folding of model proteins

We perform molecular dynamics simulations for a simple coarse-grained model of crambin placed inside of a softly repulsive sphere of radius R. The confinement makes folding at the optimal temperature slower and affects the folding scenarios, but both effects are not dramatic. The influence of crowding on folding are studied by placing several identical proteins within the sphere, denaturing them, and then by monitoring refolding. If the interactions between the proteins are dominated by the excluded volume effects, the net folding times are essentially like for a single protein. An introduction of inter-proteinic attractive contacts hinders folding when the strength of the attraction exceeds about a half of the value of the strength of the single protein contacts. The bigger the strength of the attraction, the more likely is the occurrence of aggregation and misfolding

Coarse grained description of the protein folding

We consider two- and three-dimensional lattice models of proteins which were characterized previously. We coarse grain their folding dynamics by reducing it to transitions between effective states. We consider two methods of selection of the effective states. The first method is based on the steepest descent mapping of states to underlying local energy minima and the other involves an additional projection to maximally compact conformations. Both methods generate connectivity patterns that allow to distinguish between the good and bad folders. Connectivity graphs corresponding to the folding funnel have few loops and are thus tree-like. The Arrhenius law for the median folding time of a 16-monomer sequence is established and the corresponding barrier is related to easily identifiable kinetic trap states.Comment: REVTeX, 9 pages, 15 EPS figures, to appear in Phys. Rev.

Energy landscapes, supergraphs, and "folding funnels" in spin systems

Dynamical connectivity graphs, which describe dynamical transition rates between local energy minima of a system, can be displayed against the background of a disconnectivity graph which represents the energy landscape of the system. The resulting supergraph describes both dynamics and statics of the system in a unified coarse-grained sense. We give examples of the supergraphs for several two dimensional spin and protein-related systems. We demonstrate that disordered ferromagnets have supergraphs akin to those of model proteins whereas spin glasses behave like random sequences of aminoacids which fold badly.Comment: REVTeX, 9 pages, two-column, 13 EPS figures include

Nanoindentation of virus capsids in a molecular model

A molecular-level model is used to study the mechanical response of empty cowpea chlorotic mottle virus (CCMV) and cowpea mosaic virus (CPMV) capsids. The model is based on the native structure of the proteins that consitute the capsids and is described in terms of the C-alpha atoms. Nanoindentation by a large tip is modeled as compression between parallel plates. Plots of the compressive force versus plate separation for CCMV are qualitatively consistent with continuum models and experiments, showing an elastic region followed by an irreversible drop in force. The mechanical response of CPMV has not been studied, but the molecular model predicts an order of magnitude higher stiffness and a much shorter elastic region than for CCMV. These large changes result from small structural changes that increase the number of bonds by only 30% and would be difficult to capture in continuum models. Direct comparison of local deformations in continuum and molecular models of CCMV shows that the molecular model undergoes a gradual symmetry breaking rotation and accommodates more strain near the walls than the continuum model. The irreversible drop in force at small separations is associated with rupturing nearly all of the bonds between capsid proteins in the molecular model while a buckling transition is observed in continuum models.Comment: 18 figure

Experimental Limits on Primordial Black Hole Dark Matter from the First Two Years of Kepler Data

We present the analysis on our new limits of the dark matter (DM) halo consisting of primordial black holes (PBHs) or massive compact halo objects (MACHOs). We present a search of the first two years of publicly available Kepler mission data for potential signatures of gravitational microlensing caused by these objects, as well as an extensive analysis of the astrophysical sources of background error. These include variable stars, flare events, and comets or asteroids which are moving through the Kepler field. We discuss the potential of detecting comets using the Kepler lightcurves, presenting measurements of two known comets and one unidentified object, most likely an asteroid or comet. After removing the background events with statistical cuts, we find no microlensing candidates. We therefore present our Monte Carlo efficiency calculation in order to constrain the PBH DM with masses in the range of 2 x 10^-9 solar masses to 10^-7 solar masses. We find that PBHs in this mass range cannot make up the entirety of the DM, thus closing a full order of magnitude in the allowed mass range for PBH DM.Comment: 12 pages, 6 figure

Doping effects of Co, Ni, and Cu in FeTe0.65Se0.35 single crystals

The resistivity, magnetoresistance, and magnetic susceptibility are measured in single crystals of FeTe0.65Se0.35 with Cu, Ni, and Co substitutions for Fe. The crystals are grown by Bridgman's method. The resistivity measurements show that superconductivity disappears with the rate which correlates with the nominal valence of the impurity. From magnetoresistance we evaluate doping effect on the basic superconducting parameters, such as upper critical field and coherence length. We find indications that doping leads to two component superconducting behavior, possibly because of local charge depression around impurities.Comment: 4 pages, 4 figures, 1 table, Proceedings of the XV-th National School "Hundred Years of Superconductivity", Kazimierz Dolny, October 9-13, 201

Response approach to the squeezed-limit bispectrum: application to the correlation of quasar and Lyman-α\alpha forest power spectrum

The squeezed-limit bispectrum, which is generated by nonlinear gravitational evolution as well as inflationary physics, measures the correlation of three wavenumbers, in the configuration where one wavenumber is much smaller than the other two. Since the squeezed-limit bispectrum encodes the impact of a large-scale fluctuation on the small-scale power spectrum, it can be understood as how the small-scale power spectrum "responds" to the large-scale fluctuation. Viewed in this way, the squeezed-limit bispectrum can be calculated using the response approach even in the cases which do not submit to perturbative treatment. To illustrate this point, we apply this approach to the cross-correlation between the large-scale quasar density field and small-scale Lyman-$\alpha$ forest flux power spectrum. In particular, using separate universe simulations which implement changes in the large-scale density, velocity gradient, and primordial power spectrum amplitude, we measure how the Lyman-$\alpha$ forest flux power spectrum responds to the local, long-wavelength quasar overdensity, and equivalently their squeezed-limit bispectrum. We perform a Fisher forecast for the ability of future experiments to constrain local non-Gaussianity using the bispectrum of quasars and the Lyman-$\alpha$ forest. Combining with quasar and Lyman-$\alpha$ forest power spectra to constrain the biases, we find that for DESI the expected $1-\sigma$ constraint is ${\rm err}[f_{\rm NL}]\sim60$. Ability for DESI to measure $f_{\rm NL}$ through this channel is limited primarily by the aliasing and instrumental noise of the Lyman-$\alpha$ forest flux power spectrum. The combination of response approach and separate universe simulations provides a novel technique to explore the constraints from the squeezed-limit bispectrum between different observables.Comment: 20 pages, 4 figures; matches JCAP accepted versio

Scaling of folding properties in simple models of proteins

Scaling of folding properties of proteins is studied in a toy system -- the lattice Go model with various two- and three- dimensional geometries of the maximally compact native states. Characteristic folding times grow as power laws with the system size. The corresponding exponents are not universal. Scaling of the thermodynamic stability also indicates size-related deterioration of the folding properties.Comment: REVTeX, 4 pages, 4 EPS figures, PRL (in press