Relationship between protein thermodynamic constraints and variation of evolutionary rates among sites

Evolutionary-rate variation among sites within proteins depends on functional and biophysical properties that constrain protein evolution. It is generally accepted that proteins must be able to fold stably in order to function. However, the relationship between stability constraints and among-sites rate variation is not well understood. Here, we present a biophysical model that links the thermodynamic stability changes due to mutations at sites in proteins (ΔΔG) to the rate at which mutations accumulate at those sites over evolutionary time. We find that such a 'stability model' generally performs well, displaying correlations between predicted and empirically observed rates of up to 0.75 for some proteins. We further find that our model has comparable predictive power as does an alternative, recently proposed 'stress model' that explains evolutionary-rate variation among sites in terms of the excess energy needed for mutants to adopt the correct active structure (ΔΔG∗). The two models make distinct predictions, though, and for some proteins the stability model outperforms the stress model and vice versa. We conclude that both stability and stress constrain site-specific sequence evolution in proteins.Fil: Echave, Julián. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Jackson, Eleisha L.. University of Texas at Austin; Estados UnidosFil: Wilke, Claus O.. University of Texas at Austin; Estados Unido

Dynamic charge inhomogenity in cuprate superconductors

The inelastic x-ray scattering spectrum for phonons of $\Delta_{1}$-symmetry including the CuO bond-stretching phonon dispersion is analyzed by a Lorentz fit in HgBa$_{2}$CuO$_{4}$ and Bi$_{2}$Sr$_{2}$CuO$_{6}$, respectively, using recently calculated phonon frequencies as input parameters. The resulting mode frequencies of the fit are almost all in good agreement with the calculated data. An exception is the second highest $\Delta_{1}$-branch compromising the bond-stretching modes which disagrees in both compounds with the calculations. This branch unlike the calculations shows an anomalous softening with a minimum around the wavevector \vc{q}=\frac{2\pi}{a}(0.25, 0, 0). Such a disparity with the calculated results, that are based on the assumption of an undisturbed translation- and point group invariant electronic structure of the CuO plane, indicates some {\it static} charge inhomogenities in the measured probes. Most likely these will be charge stripes along the CuO bonds which have the strongest coupling to certain longitudinal bond-stretching modes that in turn selfconsistently induce corresponding {\it dynamic} charge inhomogenities. The symmetry breaking by the mix of dynamic and static charge inhomogenities can lead to a reconstruction of the Fermi surface into small pockets.Comment: 7 pages, 4 figure

Enhancement of the Critical Current Density of YBa2Cu3Ox Superconductors under Hydrostatic Pressure

The dependence of the critical current density Jc on hydrostatic pressure to 0.6 GPa is determined for a single 25-degree [001]-tilt grain boundary in a bicrystalline ring of nearly optimally doped melt-textured YBa2Cu3Ox. Jc is found to increase rapidly under pressure at +20 %/GPa. A new diagnostic method is introduced (pressure-induced Jc relaxation) which reveals a sizeable concentration of vacant oxygen sites in the grain boundary region. Completely filling such sites with oxygen anions should lead to significant enhancements in Jc.Comment: revised manuscript, graphic errors in figures correcte

Kondo physics in tunable semiconductor nanowire quantum dots

We have observed the Kondo effect in strongly coupled semiconducting nanowire quantum dots. The devices are made from indium arsenide nanowires, grown by molecular beam epitaxy, and contacted by titanium leads. The device transparency can be tuned by changing the potential on a gate electrode, and for increasing transparencies the effects dominating the transport changes from Coulomb Blockade to Universal Conductance Fluctuations with Kondo physics appearing in the intermediate region.Comment: 4 pages, 4 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

Quantum Stress Tensor Fluctuations and their Physical Effects

We summarize several aspects of recent work on quantum stress tensor fluctuations and their role in driving fluctuations of the gravitational field. The role of correlations and anticorrelations is emphasized. We begin with a review of the properties of the stress tensor correlation function. We next consider some illuminating examples of non-gravitational effects of stress tensors fluctuations, specifically fluctuations of the Casimir force and radiation pressure fluctuations. We next discuss passive fluctuations of spacetime geometry and some of their operational signatures. These include luminosity fluctuations, line broadening, and angular blurring of a source viewed through a fluctuating gravitational field. Finally, we discuss the possible role of quantum stress tensor fluctuations in the early universe, especially in inflation. The fluctuations of the expansion of a congruence of comoving geodesics grows during the inflationary era, due to non-cancellation of anticorrelations that would have occurred in flat spacetime. This results in subsequent non-Gaussian density perturbations and allows one to infer an upper bound on the duration of inflation. This bound is consistent with adequate inflation to solve the horizon and flatness problems.Comment: 15 pages, 1 figure; invited talk presented at the 3rd Mexican Meeting on Experimental and Theoretical Physics, Mexico City, September 10-14, 200

The scalar sector in the Myers-Pospelov model

We construct a perturbative expansion of the scalar sector in the Myers-Pospelov model, up to second order in the Lorentz violating parameter and taking into account its higher-order time derivative character. This expansion allows us to construct an hermitian positive-definite Hamiltonian which provides a correct basis for quantization. Demanding that the modified normal frequencies remain real requires the introduction of an upper bound in the magnitude |k| of the momentum, which is a manifestation of the effective character of the model. The free scalar propagator, including the corresponding modified dispersion relations, is also calculated to the given order, thus providing the starting point to consider radiative corrections when interactions are introduced.Comment: Published in AIP Conf.Proc.977:214-223,200