From Nonspecific DNA–Protein Encounter Complexes to the Prediction of DNA–Protein Interactions

©2009 Gao, Skolnick. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.doi:10.1371/journal.pcbi.1000341DNA–protein interactions are involved in many essential biological activities. Because there is no simple mapping code between DNA base pairs and protein amino acids, the prediction of DNA–protein interactions is a challenging problem. Here, we present a novel computational approach for predicting DNA-binding protein residues and DNA–protein interaction modes without knowing its specific DNA target sequence. Given the structure of a DNA-binding protein, the method first generates an ensemble of complex structures obtained by rigid-body docking with a nonspecific canonical B-DNA. Representative models are subsequently selected through clustering and ranking by their DNA–protein interfacial energy. Analysis of these encounter complex models suggests that the recognition sites for specific DNA binding are usually favorable interaction sites for the nonspecific DNA probe and that nonspecific DNA–protein interaction modes exhibit some similarity to specific DNA–protein binding modes. Although the method requires as input the knowledge that the protein binds DNA, in benchmark tests, it achieves better performance in identifying DNA-binding sites than three previously established methods, which are based on sophisticated machine-learning techniques. We further apply our method to protein structures predicted through modeling and demonstrate that our method performs satisfactorily on protein models whose root-mean-square Ca deviation from native is up to 5 Å from their native structures. This study provides valuable structural insights into how a specific DNA-binding protein interacts with a nonspecific DNA sequence. The similarity between the specific DNA–protein interaction mode and nonspecific interaction modes may reflect an important sampling step in search of its specific DNA targets by a DNA-binding protein

Non-Perturbative Topological Strings And Conformal Blocks

We give a non-perturbative completion of a class of closed topological string theories in terms of building blocks of dual open strings. In the specific case where the open string is given by a matrix model these blocks correspond to a choice of integration contour. We then apply this definition to the AGT setup where the dual matrix model has logarithmic potential and is conjecturally equivalent to Liouville conformal field theory. By studying the natural contours of these matrix integrals and their monodromy properties, we propose a precise map between topological string blocks and Liouville conformal blocks. Remarkably, this description makes use of the light-cone diagrams of closed string field theory, where the critical points of the matrix potential correspond to string interaction points.Comment: 36 page

Bootstrapping the energy flow in the beginning of life.

This paper suggests that the energy flow on which all living structures depend only started up slowly, the low-energy, initial phase starting up a second, slightly more energetic phase, and so on. In this way, the build up of the energy flow follows a bootstrapping process similar to that found in the development of computers, the first generation making possible the calculations necessary for constructing the second one, etc. In the biogenetic upstart of an energy flow, non-metals in the lower periods of the Periodic Table of Elements would have constituted the most primitive systems, their operation being enhanced and later supplanted by elements in the higher periods that demand more energy. This bootstrapping process would put the development of the metabolisms based on the second period elements carbon, nitrogen and oxygen at the end of the evolutionary process rather than at, or even before, the biogenetic even

αA-crystallin R49Cneo mutation influences the architecture of lens fiber cell membranes and causes posterior and nuclear cataracts in mice

<p>Abstract</p> <p>Background</p> <p>αA-crystallin (CRYAA/HSPB4), a major component of all vertebrate eye lenses, is a small heat shock protein responsible for maintaining lens transparency. The R49C mutation in the αA-crystallin protein is linked with non-syndromic, hereditary human cataracts in a four-generation Caucasian family.</p> <p>Methods</p> <p>This study describes a mouse cataract model generated by insertion of a neomycin-resistant (neo^r) gene into an intron of the gene encoding mutant R49C αA-crystallin. Mice carrying the neo^rgene and wild-type <it>Cryaa </it>were also generated as controls. Heterozygous knock-in mice containing one wild type gene and one mutated gene for αA-crystallin (WT/R49C^neo) and homozygous knock-in mice containing two mutated genes (R49C^neo/R49C^neo) were compared.</p> <p>Results</p> <p>By 3 weeks, WT/R49C^neomice exhibited large vacuoles in the cortical region 100 μm from the lens surface, and by 3 months posterior and nuclear cataracts had developed. WT/R49C^neomice demonstrated severe posterior cataracts at 9 months of age, with considerable posterior nuclear migration evident in histological sections. R49C^neo/R49C^neomice demonstrated nearly complete lens opacities by 5 months of age. In contrast, R49C mice in which the neo^rgene was deleted by breeding with CreEIIa mice developed lens abnormalities at birth, suggesting that the neo^rgene may suppress expression of mutant R49C αA-crystallin protein.</p> <p>Conclusion</p> <p>It is apparent that modification of membrane and cell-cell interactions occurs in the presence of the αA-crystallin mutation and rapidly leads to lens cell pathology <it>in vivo</it>.</p

Measurement of the azimuthal anisotropy for charged particle production in SNN=2.76\sqrt{^{S}NN}=2.76 TeV lead-lead collisions with the ATLAS detector

Contains fulltext : 103506.pdf (preprint version ) (Open Access

Search for the standard model Higgs boson in the diphoton decay channel with 4.9fb -1 of pp collision data at √s=7TeV with atlas

A search for the standard model Higgs boson is performed in the diphoton decay channel. The data used correspond to an integrated luminosity of 4.9  fb-1 collected with the ATLAS detector at the Large Hadron Collider in proton-proton collisions at a center-of-mass energy of √s=7  TeV. In the diphoton mass range 110–150 GeV, the largest excess with respect to the background-only hypothesis is observed at 126.5 GeV, with a local significance of 2.8 standard deviations. Taking the look-elsewhere effect into account in the range 110–150 GeV, this significance becomes 1.5 standard deviations. The standard model Higgs boson is excluded at 95% confidence level in the mass ranges of 113–115 GeV and 134.5–136 GeV

Measurement of the transverse momentum distribution of [Z over γ*] bosons in proton-proton collisions at √s = 7 TeV with the ATLAS detector

A measurement of the [Z over γ*] transverse momentum (p[Z over T]) distribution in proton–proton collisions at √s = 7 TeV is presented using [Z over γ*] →e[superscript +]e[superscript −] and [Z over γ*] →μ[superscript +]μ[superscript −] decays collected with the ATLAS detector in data sets with integrated luminosities of 35 pb[superscript −1] and 40 pb[superscript −1], respectively. The normalized differential cross sections are measured separately for electron and muon decay channels as well as for their combination up to p[Z over T] of 350 GeV for invariant dilepton masses 66 GeV<m[subscript ℓℓ]<116 GeV. The measurement is compared to predictions of perturbative QCD and various event generators. The prediction of resummed QCD combined with fixed order perturbative QCD is found to be in good agreement with the data.United States. Dept. of EnergyNational Science Foundation (U.S.)Brookhaven National LaboratoryEuropean Organization for Nuclear Researc

Search for the standard model Higgs boson in the diphoton decay channel with 4.9fb -1 of pp collision data at √s=7TeV with atlas

A search for the standard model Higgs boson is performed in the diphoton decay channel. The data used correspond to an integrated luminosity of 4.9  fb-1 collected with the ATLAS detector at the Large Hadron Collider in proton-proton collisions at a center-of-mass energy of √s=7  TeV. In the diphoton mass range 110–150 GeV, the largest excess with respect to the background-only hypothesis is observed at 126.5 GeV, with a local significance of 2.8 standard deviations. Taking the look-elsewhere effect into account in the range 110–150 GeV, this significance becomes 1.5 standard deviations. The standard model Higgs boson is excluded at 95% confidence level in the mass ranges of 113–115 GeV and 134.5–136 GeV