Gauge Independence of IR singularities in Non-Commutative QFT - and Interpolating Gauges

IR divergences of a non-commutative U(1) Maxwell theory are discussed at the one-loop level using an interpolating gauge to show that quadratic IR divergences are independent not only from a covariant gauge fixing but also independent from an axial gauge fixing.Comment: 11 pages, 2 figures, v1 minor correction

A Vector Supersymmetry in Noncommutative U(1) Gauge Theory with the Slavnov Term

We consider noncommutative U(1) gauge theory with the additional term, involving a scalar field lambda, introduced by Slavnov in order to cure the infrared problem. we show that this theory, with an appropriate space-like axial gauge-fixing, wxhibits a linear vector supersymmetry similar to the one present in the 2-dimensional BF model. This vector supersymmetry implies that all loop corrections are independent of the $\lambda AA$-vertex and thereby explains why Slavnov found a finite model for the same gauge-fixing.Comment: 18 pages, 3 figures; v2 Acknowledgments adde

A Generalization of Slavnov-Extended Non-Commutative Gauge Theories

We consider a non-commutative U(1) gauge theory in 4 dimensions with a modified Slavnov term which looks similar to the 3-dimensional BF model. In choosing a space-like axial gauge fixing we find a new vector supersymmetry which is used to show that the model is free of UV/IR mixing problems, just as in the previously discussed model in arXiv:hep-th/0604154. Finally, we present generalizations of our proposed model to higher dimensions.Comment: 25 pages, no figures; v2 minor correction

On the symmetries of BF models and their relation with gravity

The perturbative finiteness of various topological models (e.g. BF models) has its origin in an extra symmetry of the gauge-fixed action, the so-called vector supersymmetry. Since an invariance of this type also exists for gravity and since gravity is closely related to certain BF models, vector supersymmetry should also be useful for tackling various aspects of quantum gravity. With this motivation and goal in mind, we first extend vector supersymmetry of BF models to generic manifolds by incorporating it into the BRST symmetry within the Batalin-Vilkovisky framework. Thereafter, we address the relationship between gravity and BF models, in particular for three-dimensional space-time.Comment: 29 page

Addressing Grand Challenges in Earth Observation Science: The Earth Observation Data Centre for Water Resources Monitoring

Earth observation is entering a new era where the increasing availability of free and open global satellite data sets combined with the computing power offered by modern information technologies opens up the possibility to process high-resolution data sets at global scale and short repeat intervals in a fully automatic fashion. This will not only boost the availability of higher level earth observation data in purely quantitative terms, but can also be expected to trigger a step change in the quality and usability of earth observation data. However, the technical, scientific, and organisational challenges that need to be overcome to arrive at this point are significant. First of all, Petabyte-scale data centres are needed for storing and processing complete satellite data records. Second, innovative processing chains that allow fully automatic processing of the satellite data from the raw sensor records to higher-level geophysical products need to be developed. Last but not least, new models of cooperation between public and private actors need to be found in order to live up to the first two challenges. This paper offers a discussion of how the Earth Observation Data Centre for Water Resources Monitoring (EODC) – a catalyser for an open and international cooperation of public and private organisations – will address these three grand challenges with the aim to foster the use of earth observation for monitoring of global water resources

Structural Anisotropy in Polar Fluids Subjected to Periodic Boundary Conditions

A heuristic model based on dielectric continuum theory for the long-range solvation free energy of a dipolar system possessing periodic boundary conditions (PBCs) is presented. The predictions of the model are compared to simulation results for Stockmayer fluids simulated using three different cell geometries. The boundary effects induced by the PBCs are shown to lead to anisotropies in the apparent dielectric constant and the long-range solvation free energy of as much as 50%. However, the sum of all of the anisotropic energy contributions yields a value that is very close to the isotropic one derived from dielectric continuum theory, leading to a total system energy close to the dielectric value. It is finally shown that the leading-order contribution to the energetic and structural anisotropy is significantly smaller in the noncubic simulation cell geometries compared to when using a cubic simulation cell

Position of the Third Na+ Site in the Aspartate Transporter GltPh and the Human Glutamate Transporter, EAAT1

Glutamate transport via the human excitatory amino acid transporters is coupled to the co-transport of three Na+ ions, one H+ and the counter-transport of one K+ ion. Transport by an archaeal homologue of the human glutamate transporters, GltPh, whose three dimensional structure is known is also coupled to three Na+ ions but only two Na+ ion binding sites have been observed in the crystal structure of GltPh. In order to fully utilize the GltPh structure in functional studies of the human glutamate transporters, it is essential to understand the transport mechanism of GltPh and accurately determine the number and location of Na+ ions coupled to transport. Several sites have been proposed for the binding of a third Na+ ion from electrostatic calculations and molecular dynamics simulations. In this study, we have performed detailed free energy simulations for GltPh and reveal a new site for the third Na+ ion involving the side chains of Threonine 92, Serine 93, Asparagine 310, Aspartate 312, and the backbone of Tyrosine 89. We have also studied the transport properties of alanine mutants of the coordinating residues Threonine 92 and Serine 93 in GltPh, and the corresponding residues in a human glutamate transporter, EAAT1. The mutant transporters have reduced affinity for Na+ compared to their wild type counterparts. These results confirm that Threonine 92 and Serine 93 are involved in the coordination of the third Na+ ion in GltPh and EAAT1

Catalytic Cycle of Multicopper Oxidases Studied by Combined Quantum- and Molecular-Mechanical Free-Energy Perturbation Methods

We have used combined quantum mechanical and molecular mechanical free-energy perturbation methods in combination with explicit solvent simulations to study the reaction mechanism of the multicopper oxidases, in particular the regeneration of the reduced state from the native intermediate. For 52 putative states of the trinuclear copper cluster, differing in the oxidation states of the copper ions and the protonation states of water- and O2-derived ligands, we have studied redox potentials, acidity constants, isomerisation reactions, as well as water- and O2 binding reactions. Thereby, we can propose a full reaction mechanism of the multicopper oxidases with atomic detail. We also show that the two copper sites in the protein communicate so that redox potentials and acidity constants of one site are affected by up to 0.2 V or 3 pKa units by a change in the oxidation state of the other site

Free Energy Simulations of a GTPase: GTP and GDP Binding to Archaeal Initiation Factor 2

International audienceArchaeal initiation factor 2 (aIF2) is a protein involved in the initiation of protein biosynthesis. In its GTP-bound, "ON" conformation, aIF2 binds an initiator tRNA and carries it to the ribosome. In its GDP-bound, "OFF" conformation, it dissociates from tRNA. To understand the specific binding of GTP and GDP and its dependence on the ON or OFF conformational state of aIF2, molecular dynamics free energy simulations (MDFE) are a tool of choice. However, the validity of the computed free energies depends on the simulation model, including the force field and the boundary conditions, and on the extent of conformational sampling in the simulations. aIF2 and other GTPases present specific difficulties; in particular, the nucleotide ligand coordinates a divalent Mg(2+) ion, which can polarize the electronic distribution of its environment. Thus, a force field with an explicit treatment of electronic polarizability could be necessary, rather than a simpler, fixed charge force field. Here, we begin by comparing a fixed charge force field to quantum chemical calculations and experiment for Mg(2+):phosphate binding in solution, with the force field giving large errors. Next, we consider GTP and GDP bound to aIF2 and we compare two fixed charge force fields to the recent, polarizable, AMOEBA force field, extended here in a simple, approximate manner to include GTP. We focus on a quantity that approximates the free energy to change GTP into GDP. Despite the errors seen for Mg(2+):phosphate binding in solution, we observe a substantial cancellation of errors when we compare the free energy change in the protein to that in solution, or when we compare the protein ON and OFF states. Finally, we have used the fixed charge force field to perform MDFE simulations and alchemically transform GTP into GDP in the protein and in solution. With a total of about 200 ns of molecular dynamics, we obtain good convergence and a reasonable statistical uncertainty, comparable to the force field uncertainty, and somewhat lower than the predicted GTP/GDP binding free energy differences. The sign and magnitudes of the differences can thus be interpreted at a semiquantitative level, and are found to be consistent with the experimental binding preferences of ON- and OFF-aIF2

Distinguishing Binders from False Positives by Free Energy Calculations: Fragment Screening Against the Flap Site of HIV Protease

Molecular docking is a powerful tool used in drug discovery and structural biology for predicting the structures of ligand–receptor complexes. However, the accuracy of docking calculations can be limited by factors such as the neglect of protein reorganization in the scoring function; as a result, ligand screening can produce a high rate of false positive hits. Although absolute binding free energy methods still have difficulty in accurately rank-ordering binders, we believe that they can be fruitfully employed to distinguish binders from nonbinders and reduce the false positive rate. Here we study a set of ligands that dock favorably to a newly discovered, potentially allosteric site on the flap of HIV-1 protease. Fragment binding to this site stabilizes a closed form of protease, which could be exploited for the design of allosteric inhibitors. Twenty-three top-ranked protein–ligand complexes from AutoDock were subject to the free energy screening using two methods, the recently developed binding energy analysis method (BEDAM) and the standard double decoupling method (DDM). Free energy calculations correctly identified most of the false positives (≥83%) and recovered all the confirmed binders. The results show a gap averaging ≥3.7 kcal/mol, separating the binders and the false positives. We present a formula that decomposes the binding free energy into contributions from the receptor conformational macrostates, which provides insights into the roles of different binding modes. Our binding free energy component analysis further suggests that improving the treatment for the desolvation penalty associated with the unfulfilled polar groups could reduce the rate of false positive hits in docking. The current study demonstrates that the combination of docking with free energy methods can be very useful for more accurate ligand screening against valuable drug targets