Interaction with specific HSP90 residues as a scoring function: validation in the D3R Grand Challenge 2015

Here is reported the development of a novel scoring function that performs remarkably well at identifying the native binding pose of a subset of HSP90 inhibitors containing aminopyrimidine or resorcinol based scaffolds. This scoring function is called PocketScore, and consists of the interaction energy between a ligand and three residues in the binding pocket: Asp93, Thr184 and a water molecule. We integrated PocketScore into a molecular docking workflow, and used it to participate in the Drug Design Data Resource (D3R) Grand Challenge 2015 (GC2015). PocketScore was able to rank 180 molecules of the GC2015 according to their binding affinity with satisfactory performance. These results indicate that the specific residues considered by PocketScore are determinant to properly model the interaction between HSP90 and its subset of inhibitors containing aminopyrimidine or resorcinol based scaffolds. Moreover, the development of PocketScore aimed at improving docking power while neglecting the prediction of binding affinities, suggesting that accurate identification of native binding poses is a determinant factor for the performance of virtual screens.     

Influence of pre-shearing on rheometric measurements of an oil-based drilling fluid

Drilling fluids are suspensions of solid particles and present thixotropic and elastoviscoplastic behaviors simultaneously, which turn their rheological characterization into a challenging task. Rotational rheometers are widely employed to determine the properties of these fluids, and one major challenge in rheometric tests carried out with thixotropic fluids is to obtain repeatable results. Submitting the fluid specimen to a known shear history by performing a pre-shear procedure is commonly used to achieve repeatable results with thixotropic fluids. In this paper, the effect of different pre-shearing conditions on the rheological measurements of an oil-based drilling fluid was investigated using cross-hatched parallel plates. Firstly, an adequate aging time to ensure complete fluid restructuring was determined by monitoring the storage modulus, G′, over an oscillatory time sweep experiment. Shear-rate controlled start-up tests were then conducted to evaluate the gel strength and the steady-state shear stress. Nine different pre-shearing conditions were evaluated, and each experiment was performed three times. Finally, the results were analyzed by using two statistical tools: a two-way analysis of variance (ANOVA) and the Tukey’s range test. The analysis shows that despite the good repeatability achieved when the same pre-shear condition is applied, the pre-shearing affects not only the gel strength but also the steady-state shear stress. The ANOVA also revealed that the effect of the pre-shearing shear rate on the fluid rheological behavior is statistically more significant than the effect of the pre-shearing time. The same analysis was performed after 10 s and 10 min of aging, and similar results were obtained.     

Scaling dynamics for a particle in a time-dependent potential well

Some dynamical properties for a classical particle confined in an infinitely deep box of potential containing a periodically oscillating square well are studied. The dynamics of the system is described by using a two-dimensional non-linear area-preserving map for the variables energy and time. The phase space is mixed and the chaotic sea is described using scaling arguments. Scaling exponents are obtained as a function of all the control parameters, extending the previous results obtained in the literature.     

Synthesis of 1,2,3-triazolylpyranosides through click chemistry reaction

We have developed an efficient method for the synthesis of functionalized C-glycosyl 1,2,3-triazoles through a Cu(I)-promoted azide–alkyne 1,3-dipolar cycloaddition between a TMS-protected C-alkynyl-glycoside and organic azides. The reaction was accelerated by ultrasound irradiation and the addition of a base was not necessary to obtain the 1,2,3-triazole product. Moreover, further manipulation of the products led to chiral molecules with a C-glycoside linkage.     

Effects of CO<Subscript>2</Subscript> Compressibility on CO<Subscript>2</Subscript> Storage in Deep Saline Aquifers

The injection of supercritical CO₂ in deep saline aquifers leads to the formation of a CO₂ plume that tends to float above the formation brine. As pressure builds up, CO₂ properties, i.e. density and viscosity, can vary significantly. Current analytical solutions do not account for CO₂ compressibility. In this article, we investigate numerically and analytically the effect of this variability on the position of the interface between the CO₂-rich phase and the formation brine. We introduce a correction to account for CO₂ compressibility (density variations) and viscosity variations in current analytical solutions. We find that the error in the interface position caused by neglecting CO₂ compressibility is relatively small when viscous forces dominate. However, it can become significant when gravity forces dominate, which is likely to occur at late times of injection.     

Organocatalytic asymmetric aldol reactions mediated by a cysteine-derived prolinamide

In this Letter, a cysteine-derived prolinamide is described to act as a robust and effective organocatalyst for enantioselective aldol reactions.     

Error Estimates for the Approximation of the Effective Hamiltonian

We study approximation schemes for the cell problem arising in homogenization of Hamilton-Jacobi equations. We prove several error estimates concerning the rate of convergence of the approximation scheme to the effective Hamiltonian, both in the optimal control setting and as well as in the calculus of variations setting. D.G. was partially supported by the Center for Mathematical Analysis, Geometry and Dynamical Systems through FCT Program POCTI/FEDER and by grant POCI/FEDER/MAT/55745/2004.     

Synthesis of dihydrofuran rings using α‐substituted β‐ketoamides

In this paper is described an unreported method employing α‐alkenyl β‐ketoamides as starting material to give 2,3‐dihydrofurans, precursors of substituted furans.