Functional Sites Induce Long-Range Evolutionary Constraints in Enzymes

Functional residues in proteins tend to be highly conserved over evolutionary time. However, to what extent functional sites impose evolutionary constraints on nearby or even more distant residues is not known. Here, we report pervasive conservation gradients toward catalytic residues in a dataset of 524 distinct enzymes: evolutionary conservation decreases approximately linearly with increasing distance to the nearest catalytic residue in the protein structure. This trend encompasses, on average, 80% of the residues in any enzyme, and it is independent of known structural constraints on protein evolution such as residue packing or solvent accessibility. Further, the trend exists in both monomeric and multimeric enzymes and irrespective of enzyme size and/or location of the active site in the enzyme structure. By contrast, sites in protein–protein interfaces, unlike catalytic residues, are only weakly conserved and induce only minor rate gradients. In aggregate, these observations show that functional sites, and in particular catalytic residues, induce long-range evolutionary constraints in enzymes.Fil: Jack, Benjamin R.. University of Texas at Austin; Estados UnidosFil: Meyer, Austin G.. University of Texas at Austin; Estados UnidosFil: Echave, Julián. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Wilke, Claus O.. University of Texas at Austin; Estados Unido

Strong magnetoresistance induced by long-range disorder

We calculate the semiclassical magnetoresistivity $\rho_{xx}(B)$ of non-interacting fermions in two dimensions moving in a weak and smoothly varying random potential or random magnetic field. We demonstrate that in a broad range of magnetic fields the non-Markovian character of the transport leads to a strong positive magnetoresistance. The effect is especially pronounced in the case of a random magnetic field where $\rho_{xx}(B)$ becomes parametrically much larger than its B=0 value.Comment: REVTEX, 4 pages, 2 eps figure

Zero-frequency anomaly in quasiclassical ac transport: Memory effects in a two-dimensional metal with a long-range random potential or random magnetic field

We study the low-frequency behavior of the {\it ac} conductivity $\sigma(\omega)$ of a two-dimensional fermion gas subject to a smooth random potential (RP) or random magnetic field (RMF). We find a non-analytic $\propto|\omega|$ correction to ${\rm Re} \sigma$, which corresponds to a $1/t^2$ long-time tail in the velocity correlation function. This contribution is induced by return processes neglected in Boltzmann transport theory. The prefactor of this $|\omega|$-term is positive and proportional to $(d/l)^2$ for RP, while it is of opposite sign and proportional to $d/l$ in the weak RMF case, where $l$ is the mean free path and $d$ the disorder correlation length. This non-analytic correction also exists in the strong RMF regime, when the transport is of a percolating nature. The analytical results are supported and complemented by numerical simulations.Comment: 12 pages, RevTeX, 7 figure

Analyzing Machupo virus-receptor binding by molecular dynamics simulations

In many biological applications, we would like to be able to computationally predict mutational effects on affinity in protein-protein interactions. However, many commonly used methods to predict these effects perform poorly in important test cases. In particular, the effects of multiple mutations, non-alanine substitutions, and flexible loops are difficult to predict with available tools and protocols. We present here an existing method applied in a novel way to a new test case; we interrogate affinity differences resulting from mutations in a host-virus protein-protein interface. We use steered molecular dynamics (SMD) to computationally pull the machupo virus (MACV) spike glycoprotein (GP1) away from the human transferrin receptor (hTfR1). We then approximate affinity using the maximum applied force of separation and the area under the force-versus-distance curve. We find, even without the rigor and planning required for free energy calculations, that these quantities can provide novel biophysical insight into the GP1/hTfR1 interaction. First, with no prior knowledge of the system we can differentiate among wild type and mutant complexes. Moreover, we show that this simple SMD scheme correlates well with relative free energy differences computed via free energy perturbation. Second, although the static co-crystal structure shows two large hydrogen-bonding networks in the GP1/hTfR1 interface, our simulations indicate that one of them may not be important for tight binding. Third, one viral site known to be critical for infection may mark an important evolutionary suppressor site for infection-resistant hTfR1 mutants. Finally, our approach provides a framework to compare the effects of multiple mutations, individually and jointly, on protein-protein interactions.Comment: 33 pages, 8 figures, 5 table

Re-entrant ferroelectricity in liquid crystals

The ferroelectric (Sm C$^*$) -- antiferroelectric (Sm C$^*_A$) -- reentrant ferroelectric (re Sm C$^*$) phase temperature sequence was observed for system with competing synclinic - anticlinic interactions. The basic properties of this system are as follows (1) the Sm C$^*$ phase is metastable in temperature range of the Sm C$^*_A$ stability (2) the double inversions of the helix handedness at Sm C$^*$ -- Sm C$^*_A$ and Sm C$^*_A$% -- re-Sm C$^*$ phase transitions were found (3) the threshold electric field that is necessary to induce synclinic ordering in the Sm C$^*_A$ phase decreases near both Sm C$^*_A$ -- Sm C$^*$ and Sm C$^*_A$ -- re-Sm C$^*$ phase boundaries, and it has maximum in the middle of the Sm C$^*_A$ stability region. All these properties are properly described by simple Landau model that accounts for nearest neighboring layer steric interactions and quadrupolar ordering only.Comment: 10 pages, 5 figures, submitted to PR

Systematic study of the two band/two gap superconductivity in carbon-substituted MgB2 by point-contact spectroscopy

Point-contact measurements on the carbon-substituted Mg(B$_{1-x}$C$_x$)$_2$ filament/powder samples directly reveal a retention of the two superconducting energy gaps in the whole doping range from $x = 0$ to $x \approx 0.1$. The large gap on the $\sigma$-band is decreased in an essentially linear fashion with increasing the carbon concentrations. The changes in the the small gap $\Delta_{\pi}$ up to 3.8 % C are proportionally smaller and are more difficult to detect but for the heavily doped sample with $x \approx 0.1$ and $T_c = 22$ K both gaps are still present, and significantly reduced, consistent with a strong essentially linear, reduction of each gap with the transition temperature.Comment: 5 eps figure

The comet 17P/Holmes 2007 outburst: the early motion of the outburst material

Context. On October 24, 2007 the periodic comet 17P/Holmes underwent an astonishing outburst that increased its apparent total brightness from magnitude V\sim17 up to V\sim2.5 in roughly two days. We report on Wendelstein 0.8 m telescope (WST) photometric observations of the early evolution stages of the outburst. Aims. We studied the evolution of the structure morphology, its kinematic, and estimated the ejected dust mass. Methods. We analized 126 images in the BVRI photometric bands spread between 26/10/2007 and 20/11/2007. The bright comet core appeared well separated from that one of a quickly expanding dust cloud in all the data, and the bulk of the latter was contained in the field of view of our instrument. The ejected dust mass was derived on the base of differential photometry on background stars occulted by the moving cloud. Results. The two cores were moving apart from each other at a relative projected constant velocity of (9.87 +/- 0.07) arcsec/day (0.135 +/-0.001 km/sec). In the inner regions of the dust cloud we observed a linear increase in size at a mean constant velocity of (14.6+/-0.3) arcsec/day (0.200+/-0.004 km/sec). Evidence of a radial velocity gradient in the expanding cloud was also found. Our estimate for the expanding coma's mass was of the order of 10^{-2}-1 comet's mass implying a significant disintegration event. Conclusions. We interpreted our observations in the context of an explosive scenario which was more probably originated by some internal instability processes, rather than an impact with an asteroidal body. Due to the peculiar characteristics of this event, further observations and investigations are necessary in order to enlight the nature of the physical processes that determined it.Comment: 5 pages, 3 figures, A&A accepte

Split dimensional regularization for the Coulomb gauge at two loops

We evaluate the coefficients of the leading poles of the complete two-loop quark self-energy \Sigma(p) in the Coulomb gauge. Working in the framework of split dimensional regularization, with complex regulating parameters \sigma and n/2-\sigma for the energy and space components of the loop momentum, respectively, we find that split dimensional regularization leads to well-defined two-loop integrals, and that the overall coefficient of the leading pole term for \Sigma(p) is strictly local. Extensive tables showing the pole parts of one- and two-loop Coulomb integrals are given. We also comment on some general implications of split dimensional regularization, discussing in particular the limit \sigma \to 1/2 and the subleading terms in the epsilon-expansion of noncovariant integrals.Comment: 32 pages Latex; figures replaced, text unchange