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

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

Molecular jamming - the cystine slipknot mechanical clamp in all-atom simulations

A recent survey of 17 134 proteins has identified a new class of proteins which are expected to yield stretching induced force-peaks in the range of 1 nN. Such high force peaks should be due to forcing of a slip-loop through a cystine ring, i.e. by generating a cystine slipknot. The survey has been performed in a simple coarse grained model. Here, we perform all-atom steered molecular dynamics simulations on 15 cystine knot proteins and determine their resistance to stretching. In agreement with previous studies within a coarse grained structure based model, the level of resistance is found to be substantially higher than in proteins in which the mechanical clamp operates through shear. The large stretching forces arise through formation of the cystine slipknot mechanical clamp and the resulting steric jamming. We elucidate the workings of such a clamp in an atomic detail. We also study the behavior of five top strength proteins with the shear-based mechanostability in which no jamming is involved. We show that in the atomic model, the jamming state is relieved by moving one amino acid at a time and there is a choice in the selection of the amino acid that advances the first. In contrast, the coarse grained model also allows for a simultaneous passage of two amino acids

Delineation of the Native Basin in Continuum Models of Proteins

We propose two approaches for determining the native basins in off-lattice models of proteins. The first of them is based on exploring the saddle points on selected trajectories emerging from the native state. In the second approach, the basin size can be determined by monitoring random distortions in the shape of the protein around the native state. Both techniques yield the similar results. As a byproduct, a simple method to determine the folding temperature is obtained.Comment: REVTeX, 6 pages, 5 EPS figure

Force-induced unfolding of a homopolymer on fractal lattice: exact results vs. mean field predictions

We study the force-induced unfolding of a homopolymer on the three dimensional Sierpinski gasket. The polymer is subject to a contact energy between nearest neighbour sites not consecutive along the chain and to a stretching force. The hierarchical nature of the lattice we consider allows for an exact treatment which yields the phase diagram and the critical behaviour. We show that for this model mean field predictions are not correct, in particular in the exact phase diagram there is {\em not} a low temperature reentrance and we find that the force induced unfolding transition below the theta temperature is second order.Comment: 15 pages, 5 eps figure

Rate Determining Factors in Protein Model Structures

Previous research has shown a strong correlation of protein folding rates to the native state geometry, yet a complete explanation for this dependence is still lacking. Here we study the rate-geometry relationship with a simple statistical physics model, and focus on two classes of model geometries, representing ideal parallel and antiparallel structures. We find that the logarithm of the rate shows an almost perfect linear correlation with the "absolute contact order", but the slope depends on the particular class considered. We discuss these findings in the light of experimental results.Comment: 4 pages, 2 figure