Strings from N=2N=2 Gauged Wess-Zumino-Witten Models

We present an algebraic approach to string theory. An embedding of $sl(2|1)$ in a super Lie algebra together with a grading on the Lie algebra determines a nilpotent subalgebra of the super Lie algebra. Chirally gauging this subalgebra in the corresponding Wess-Zumino-Witten model, breaks the affine symmetry of the Wess-Zumino-Witten model to some extension of the $N=2$ superconformal algebra. The extension is completely determined by the $sl(2|1)$ embedding. The realization of the superconformal algebra is determined by the grading. For a particular choice of grading, one obtains in this way, after twisting, the BRST structure of a string theory. We classify all embeddings of $sl(2|1)$ into Lie super algebras and give a detailed account of the branching of the adjoint representation. This provides an exhaustive classification and characterization of both all extended $N=2$ superconformal algebras and all string theories which can be obtained in this way.Comment: 50 pages, LaTe

Superstrings from Hamiltonian Reduction

In any string theory there is a hidden, twisted superconformal symmetry algebra, part of which is made up by the BRST current and the anti-ghost. We investigate how this algebra can be systematically constructed for strings with $N\!-\!2$ supersymmetries, via quantum Hamiltonian reduction of the Lie superalgebras $osp(N|2)$. The motivation is to understand how one could systematically construct generalized string theories from superalgebras. We also briefly discuss the BRST algebra of the topological string, which is a doubly twisted $N\!=\!4$ superconformal algebra.Comment: 32p, LaTeX, CERN-TH.7379/9

On the Lagrangian Realization of Non-Critical W{\cal W}-Strings

A large class of non-critical string theories with extended worldsheet gauge symmetry are described by two coupled, gauged Wess-Zumino-Witten Models. We give a detailed analysis of the gauge invariant action and in particular the gauge fixing procedure and the resulting BRST symmetries. The results are applied to the example of ${\cal W}_3$ strings.Comment: 19 pages, LaTeX (REVTEX macro's

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

Lectures on conformal field theory and Kac-Moody algebras

This is an introduction to the basic ideas and to a few further selected topics in conformal quantum field theory and in the theory of Kac-Moody algebras.Comment: 59 pages, LaTeX2e, extended version of lectures given at the Graduate Course on Conformal Field Theory and Integrable Models (Budapest, August 1996), to appear in Springer Lecture Notes in Physic

Differential stability of 2′F-ANA•RNA and ANA•RNA hybrid duplexes: roles of structure, pseudohydrogen bonding, hydration, ion uptake and flexibility

Hybrids of RNA with arabinonucleic acids 2′F-ANA and ANA have very similar structures but strikingly different thermal stabilities. We now present a thorough study combining NMR and other biophysical methods together with state-of-the-art theoretical calculations on a fully modified 10-mer hybrid duplex. Comparison between the solution structure of 2′F-ANA•RNA and ANA•RNA hybrids indicates that the increased binding affinity of 2′F-ANA is related to several subtle differences, most importantly a favorable pseudohydrogen bond (2′F–purine H8) which contrasts with unfavorable 2′-OH–nucleobase steric interactions in the case of ANA. While both 2′F-ANA and ANA strands maintained conformations in the southern/eastern sugar pucker range, the 2′F-ANA strand’s structure was more compatible with the A-like structure of a hybrid duplex. No dramatic differences are found in terms of relative hydration for the two hybrids, but the ANA•RNA duplex showed lower uptake of counterions than its 2′F-ANA•RNA counterpart. Finally, while the two hybrid duplexes are of similar rigidities, 2′F-ANA single strands may be more suitably preorganized for duplex formation. Thus the dramatically increased stability of 2′F-ANA•RNA and ANA•RNA duplexes is caused by differences in at least four areas, of which structure and pseudohydrogen bonding are the most important

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

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

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

Temperature dependence of protein dynamics simulated with three different water models

The effect of variation of the water model on the temperature dependence of protein and hydration water dynamics is examined by performing molecular dynamics simulations of myoglobin with the TIP3P, TIP4P, and TIP5P water models and the CHARMM protein force field at temperatures between 20 and 300 K. The atomic mean-square displacements, solvent reorientational relaxation times, pair angular correlations between surface water molecules, and time-averaged structures of the protein are all found to be similar, and the protein dynamical transition is described almost indistinguishably for the three water potentials. The results provide evidence that for some purposes changing the water model in protein simulations without a loss of accuracy may be possible