Docking of noncompetitive inhibitors into dengue virus type 2 protease: understanding the interactions with allosteric binding sites

A group of flavanones and their chalcones, isolated from Boesenbergia rotunda L., were previously reported to show varying degrees of noncompetitive inhibitory activities toward Dengue virus type 2 (Den2) protease. Results obtained from automated docking studies are in agreement with experimental data in which the ligands were shown to bind to sites other than the active site of the protease. The calculated K(i) values are very small, indicating that the ligands bind quite well to the allosteric binding site. Greater inhibition by pinostrobin, compared to the other compounds, can be explained by H-bonding interaction with the backbone carbonyl of Lys74, which is bonded to Asp75 (one of the catalytic triad residues). In addition, structure-activity relationship analysis yields structural information that may be useful for designing more effective therapeutic drugs against dengue virus infections.     

Palladium-Catalyzed Carbonylative Difunctionalization of Unactivated Alkenes Initiated by Unstabilized Enolates

This report describes the first example of palladium-catalyzed carbonylative difunctionalization of unactivated alkenes initiated by enolate nucleophiles. The approach involves initiation by an unstabilized enolate nucleophile under an atmospheric pressure of CO and termination with a carbon electrophile. This process is compatible with a diverse range of electrophiles, including aryl, heteroaryl, and vinyl iodides to yield synthetically useful 1,5-diketone products, which were demonstrated to be precursors for multi-substituted pyridines. A Pd^I-dimer complex with two bridging CO units was observed although its role in catalysis is not yet understood.     

Fitting PAC spectra with stochastic models: PolyPacFit

PolyPacFit is an advanced fitting program for time-differential perturbed angular correlation (PAC) spectroscopy. It incorporates stochastic models and provides robust options for customization of fits. Notable features of the program include platform independence and support for (1) fits to stochastic models of hyperfine interactions, (2) user-defined constraints among model parameters, (3) fits to multiple spectra simultaneously, and (4) any spin nuclear probe.     

On the estimation of topological entropy

We study a method for estimating the topological entropy of a smooth dynamical system. Our method is based on estimating the logarithmic growth rates of suitably chosen curves in the system. We present two algorithms for this purpose and we analyze each according to its strengths and pitfalls. We also contrast these with a method based on the definition of topological entropy, using(n, )-spanning sets.