Controlling crystal surface termination by cleavage direction

We have investigated the cleaving behavior of potassium bichromate (K(2)Cr(2)O(7)) crystals using atomic force microscopy. This crystal has a double layered AB structure along [001]. We find that, upon cleavage along the [001] plane in the <100> directions, one side is completely A terminated, while the other is B terminated. Moreover, the cleavage plane (between an A and a B layer, or between B and A) depends on the imposed direction of cleavage, i.e., [100] or [*100]. This means that the molecular layer that terminates the crystal surface can be controlled by choosing the macroscopic direction of the cleavage force. One of the two terminations is metastable and partly reconstructs to the stable termination.     

Molden 2.0: quantum chemistry meets proteins

Since the first distribution of Molden in 1995 and the publication of the first article about this software in 2000 work on Molden has continued relentlessly. A few of the many improved or fully novel features such as improved and broadened support for quantum chemistry calculations, preparation of ligands for use in drug design related softwares, and working with proteins for the purpose of ligand docking.     

Snooker: a structure-based pharmacophore generation tool applied to class A GPCRs

G-protein coupled receptors (GPCRs) are important drug targets for various diseases and of major interest to pharmaceutical companies. The function of individual members of this protein family can be modulated by the binding of small molecules at the extracellular side of the structurally conserved transmembrane (TM) domain. Here, we present Snooker, a structure-based approach to generate pharmacophore hypotheses for compounds binding to this extracellular side of the TM domain. Snooker does not require knowledge of ligands, is therefore suitable for apo-proteins, and can be applied to all receptors of the GPCR protein family. The method comprises the construction of a homology model of the TM domains and prioritization of residues on the probability of being ligand binding. Subsequently, protein properties are converted to ligand space, and pharmacophore features are generated at positions where protein ligand interactions are likely. Using this semiautomated knowledge-driven bioinformatics approach we have created pharmacophore hypotheses for 15 different GPCRs from several different subfamilies. For the beta-2-adrenergic receptor we show that ligand poses predicted by Snooker pharmacophore hypotheses reproduce literature supported binding modes for ～75% of compounds fulfilling pharmacophore constraints. All 15 pharmacophore hypotheses represent interactions with essential residues for ligand binding as observed in mutagenesis experiments and compound selections based on these hypotheses are shown to be target specific. For 8 out of 15 targets enrichment factors above 10-fold are observed in the top 0.5% ranked compounds in a virtual screen. Additionally, prospectively predicted ligand binding poses in the human dopamine D3 receptor based on Snooker pharmacophores were ranked among the best models in the community wide GPCR dock 2010.     

Surface alloying and anomalous diffusion of Bi on Cu(1 1 1)

We have used Low-Energy Electron Microscopy (LEEM) to study the formation and structure of the surface alloy of Bi on the Cu(1 1 1) surface. As a function of Bi coverage we find a progression from a dilute surface alloy to a structure, which coexists with a Bi overlayer when the Bi coverage exceeds 1/3 ML. At a temperature of 401 K, an unusual formation of alloy domains is observed. The origin of this effect is traced down to the mobility of Bi adatoms, which is found to strongly depend on the Bi coverage of the surface alloy on which they reside.     

Monolayer and aggregate formation of a modified phthalocyanine on mica determined by a delicate balance of surface interactions

An ordered layer of a phthalocyanine modified with ether tails can be formed on muscovite mica if removed from solution and dried. This ordered layer forms on potassium terminated as well as on sodium terminated mica, but not on a hydronium terminated surface. The molecules lie flat on the surface, as shown by AFM and X-ray diffraction, giving a layer thickness of approximately 1 nm. In solution, however, no in-plane ordering exists. The material is attracted to the substrate surface but instead of ordering, it aggregates in a liquid-like mobile fashion. This is likely caused by the fact that the water present in solution has a stronger interaction with the potassium ions on the mica surface than with the ether tails of the phthalocyanine.