Effect of pH and ligand charge state on BACE-1 fragment docking performance

In this work we propose a protocol for estimating the effect of pH on the docking performance to BACE-1, which affords the charge state of the inhibitor as well as the protonation state of all ionisable residues in the protein at a given pH value. To the best of our knowledge, this is the first report of a protocol predicting the BACE-1 ligand docking poses not only at the neutral pH at which most crystallographic structures were obtained, but also at the optimal pH of the enzyme (in the acidic range), at which most of the BACE-1 binding affinity assays are performed. We have applied this protocol to a set of 23 fragment-like BACE-1 ligands that span four orders of magnitude in their binding affinities. The pK _a values of the BACE-1 acidic residues deviate substantially from the estimates for model compounds in solution and display a ligand dependent variability, especially in the case of the catalytic Asp dyad residues. This outcome should have a strong bearing on the design of protocols for docking based BACE-1 screening campaigns. Finally, we were able to find an explanation for the poor docking success rate of some fragments based on the availability of anchoring points, a rationale that could help to improve hit rates in BACE-1 screening campaigns.     

Bestimmung von Blei in Erzen

Ohne ZusammenfassungAus dem Englischen übersetzt von der Redaction.     

Ambipolar hexa-peri-hexabenzocoronene-fullerene hybrid materials

A new class of self-assembling hexa-peri-hexbenzocoronene (HBC)-fullerene hybrid materials has been synthesized and characterized. Photoluminescence experiments indicate that energy transfer processes can be tuned in these donor-acceptor systems by varying the length and nature of the linker group. In preliminary device testing, ambipolar charge transport behavior is observed in organic field effect transistors, while single active component organic photovoltaic devices consisting of these materials achieved a maximum external quantum efficiency of 30%.     

Service stage Petri net models with product form solution

A class of service stage Petri net models whose equilibrium probabilities satisfy local balance equations is presented. Examples of their applicability include bus oriented multiprocessor interconnections, the classical dining philosophers problem and the alternating bit protocol. The natural topological space for embedding the state transition lattice for this class of SSPN is shown to be a multidimensional toroidal manifold.     

A Stark future for quantum control

We present an overview of developments using the nonresonant dynamic Stark effect within the fields of time-resolved molecular dynamics and quantum control, drawing on examples from our own recent work. Particular emphasis is placed on the notion that "dynamics" and "control" are not distinct disciplines and that a clear synergy exits between these areas which has, up to now, been somewhat underexploited. The dynamic Stark effect is a universal interaction which we expect to have broad applicability.     

Robust numerical analysis of the dynamic bubble formation process in a viscous liquid

The dynamics of bubble formation from a submerged nozzle in a highly viscous liquid with relatively fast inflow gas velocity is studied numerically. The numerical simulations are carried out using a sharp interface coupled level set/volume-of-fluid (CLSVOF) method and the governing equations are solved through a hydrodynamic scheme with formal second-order accuracy. Numerical results agree well with experimental results and it is shown that the sharp interface CLSVOF method enables one to reproduce the bubble formation process for a wide range of inflow gas velocities. From numerical results, one can improve their understanding of the mechanisms regarding the dynamics of bubble formation. For example, it is found that for some sets of parameters that the bubble formation process reaches steady state after several bubbles are released from the nozzle. At steady state, bubbles uniformly rise freely in the viscous liquid. It is observed that the fluid flow around a formed bubble has a significant role in determining the overall dynamic process of bubble formation; e.g. the effect of the fluid flow from the preceding bubble can be seen on newly formed bubbles.