PI by NMR: Probing CH–π Interactions in Protein–Ligand Complexes by NMR Spectroscopy

While CH–π interactions with target proteins are crucial determinants for the affinity of arguably every drug molecule, no method exists to directly measure the strength of individual CH–π interactions in drug–protein complexes. Herein, we present a fast and reliable methodology called PI (π interactions) by NMR, which can differentiate the strength of protein–ligand CH–π interactions in solution. By combining selective amino-acid side-chain labeling with ¹H-¹³C NMR, we are able to identify specific protein protons of side-chains engaged in CH–π interactions with aromatic ring systems of a ligand, based solely on ¹H chemical-shift values of the interacting protein aromatic ring protons. The information encoded in the chemical shifts induced by such interactions serves as a proxy for the strength of each individual CH–π interaction. PI by NMR changes the paradigm by which chemists can optimize the potency of drug candidates: direct determination of individual π interactions rather than averaged measures of all interactions.     

Holditch-Sätze für Regelflächen bzw. sphärische Kurven

In this paper we present some results (similar to the Holditch theorem) about the total torsion and total curvature of closed ruled surfaces resp. the area and length of closed spherical curves.     

Formation and manipulation of discrete supramolecular azobenzene assemblies

Azobenzene derivatives were deposited onto a Au(111) surface and studied by scanning tunneling microscopy. The symmetry of the parent azobenzene was broken by introducing tert-butyl groups which are known to decouple the molecular core from the substrate, on the one end, and carboxylic acid groups which direct and stabilize the supramolecular assembly structure on the surface by intermolecular hydrogen bonding, on the other end. As a consequence of the interacting COOH groups, the molecules assemble on the surface either in extended, polymeric chains and/or in discrete, hexameric rosettes. The high stability of the rosette structure is proven experimentally by controlled lateral displacement on the surface without breaking the non-covalent interactions. Although switching attempts were not successful, the approach herein should facilitate the construction of well-defined multi-switch arrays. Electronic Supplementary Material  The online version of this article () contains supplementary material, which is available to authorized users.     

A Meshless Boundary Method for Computation of Stokes Flow with Particles in the Semicircular Canals of the Inner Ear

Benign paroxismal positional vertigo (BPPV) is modeled by introducing free-floating particles (canaliths) which settle inside the semicircular canals (SCC). The Stokes flow induced by a canalith is evaluated by coupling the force coupling method (FCM) to the method of fundamental solutions (MFS). The proposed methodology results in a straightforward meshless boundary method for the simulation of bounded Stokes flow with finite-size particles. (© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim)     

A Parallel Code for LES of Compressible Swirling Jet Flow Undergoing Vortex Breakdown

Swirling jets undergoing vortex breakdown occur in many technical applications, e.g. vortex burners, turbines and jet engines. To simulate the highly nonlinear dynamics of the flow, it is necessary to use high-order numerical methods, leading to increased computational cost. To be able to perform simulations in acceptable turn-around time, an available LES code for solving the filtered compressible Navier-Stokes equations in cylindrical coordinates using compact finite-difference schemes was parallelized for massively-parallel architectures. The parallelization was done following the ghost-cell approach for filtering in the three spatial directions. The inter-process communication is handled using the message passing interface (MPI). The weak and strong scaling properties of the code indicate that it can be used for massively parallel simulations using several thousand processors. (© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim)