Probing the glycosidic linkage: UV and IR ion-dip spectroscopy of a lactoside

The beta(1-->4) glycosidic linkage found in lactose is a prevalent structural motif in many carbohydrates and glycoconjugates. Using UV and IR ion-dip spectroscopies to probe benzyl lactoside isolated in the gas phase, we find that the disaccharide unit adopts only a single, rigid structure. Its fully resolved infrared ion-dip spectrum is in excellent agreement with that of the global minimum structure computed ab initio. This has glycosidic torsion angles of phi(H) (H1-C1-O-C4') approximately 180 degrees and psi(H) (C1-O-C4'-H4') approximately 0 degrees which correspond to a rotation of approximately 150 degrees about the glycosidic bond compared to the accepted solution-phase conformation. We discuss the biological implications of this discovery and the generality of the strategies employed in making it.     

Transfer matrix analysis of the two-dimensional ANNNI model

The two-dimensional axial next-nearest neighbour Ising (ANNNI) model is studied for the first time by a transfer matrix method for semi-infinite strips (N×;N13). One obtains the thermodynamic properties and, more important, the correlation functions, which display directly the various magnetic structures. In one part of the phase diagram where a disorder line is believed to follow closely the ferromagnetic transition line the critical exponents appear to deviate from the expected ones. ForN13 a variational procedure is proposed.     

The influence of a surface on Ising and conjugate model spin correlations atT=T c

We calculate rigorously the two-point correlation function in the 2-d Ising model on a quasi-cylindrical lattice at the critical temperatureT _c .The scaling predictions for the surface critical exponents = 5/8, = 1 are confirmed and the change from surface to bulk behavior is studied. By a correspondence relation the results are mapped to the conjugate model, a subcase of the 8-vertex model. We find in this model = 5/4, = 2.     

Building up key segments of N-glycans in the gas phase: intrinsic structural preferences of the alpha(1,3) and alpha(1,6) dimannosides

The intrinsic conformer specific vibrational spectra of two important subunits of the core pentasaccharide of N-linked glycans, the alpha(1,3) and alpha(1,6) dimannosides, have been recorded in the gas phase. Coupling these measurements with a computational exploration of their conformational landscapes has enabled their conformational assignment and has identified characteristic vibrational signatures associated with particular conformational families-including those that do or do not display inter-ring hydrogen bonding across the glycosidic linkage. In addition, the IR spectra of the monosaccharide moieties provide benchmarks, through which the conformational assignments can be refined. This introduces a general concept of modularity and secondary structure in oligosaccharides--essential for the success of similar studies on larger oligosaccharides in the future.     

Engineering protein therapeutics: predictive performances of a structure-based virtual affinity maturation protocol

The implementation of a structure based virtual affinity maturation protocol and evaluation of its predictivity are presented. The in silico protocol is based on conformational sampling of the interface residues (using the Dead End Elimination/A* algorithm), followed by the estimation of the change of free energy of binding due to a point mutation, applying MM/PBSA calculations. Several implementations of the protocol have been evaluated for 173 mutations in 7 different protein complexes for which experimental data were available: the use of the Boltzamnn averaged predictor based on the free energy of binding (ΔΔG(*)) combined with the one based on its polar component only (ΔΔE(pol*)) led to the proposal of a subset of mutations out of which 45% would have successfully enhanced the binding. When focusing on those mutations that are less likely to be introduced by natural in vivo maturation methods (99 mutations with at least two base changes in the codon), the success rate is increased to 63%. In another evaluation, focusing on 56 alanine scanning mutations, the in silico protocol was able to detect 89% of the hot-spots.     

Evidence for Cluster Orbital Formation in CsSn2X5 Compounds (X=Cl, Br)

The formation of cluster orbitals in CsSn₂Br₅ is discussed and related more generally to tetragonal compounds of the type AB₂X₅ (A=monovalent cation; B=Sn, Pb; X=Cl, Br, I). The crystal structures of CsSn₂Cl₅ and CsSn₂Br₅ have been solved by single-crystal X-ray diffraction. These compounds are isostructural with each other and a range of AB₂X₅ structural analogues. In many AB₂X₅ compounds where B is a subvalent main group metal a tetragonal cell is observed with space group I4/mcm. The structures of CsSn₂Br₅ and CsSn₂Cl₅ are layered with polymeric sheets of [Sn₂X₅]ⁿ⁻_n separated by the Cs⁺ cations. Stereochemical considerations suggest that stabilization of this structural form, rather than the more ionic NH₄Pb₂Cl₅ or NaSn₂Cl₅ structures, is through interaction of the “nonbonding” valence electron pairs on tin with low-lying empty d-orbitals on neighboring X atoms. Electronic structure calculations based on the structural data confirm the likelihood of cluster orbital formation. Crystal data: CsSn₂Cl₅, tetragonal, I4/mcm, a=8.153(1) Å, c=14.882(4) Å, Z=4, R₁=0.0215, wR₂=0.0503 [I>2σ(I)], R₁=0.0393, wR₂=0.0536 (all data); CsSn₂Br₅, tetragonal, I4/mcm, a=8.483(6) Å, c=15.28(2) Å, Z=4, R₁=0.0607, wR₂=0.1411 [(I>2σ(I)], R₁=0.1579, wR₂=0.1677 (all data).