Binding Free Energy (BFE) Calculations and Quantitative Structure–Activity Relationship (QSAR) Analysis of Schistosoma mansoni Histone Deacetylase 8 (smHDAC8) Inhibitors

Histone-modifying proteins have been identified as promising targets to treat several diseases including cancer and parasitic ailments. In silico methods have been incorporated within a variety of drug discovery programs to facilitate the identification and development of novel lead compounds. In this study, we explore the binding modes of a series of benzhydroxamates derivatives developed as histone deacetylase inhibitors of Schistosoma mansoni histone deacetylase (smHDAC) using molecular docking and binding free energy (BFE) calculations. The developed docking protocol was able to correctly reproduce the experimentally established binding modes of resolved smHDAC8–inhibitor complexes. However, as has been reported in former studies, the obtained docking scores weakly correlate with the experimentally determined activity of the studied inhibitors. Thus, the obtained docking poses were refined and rescored using the Amber software. From the computed protein–inhibitor BFE, different quantitative structure–activity relationship (QSAR) models could be developed and validated using several cross-validation techniques. Some of the generated QSAR models with good correlation could explain up to ~73% variance in activity within the studied training set molecules. The best performing models were subsequently tested on an external test set of newly designed and synthesized analogs. In vitro testing showed a good correlation between the predicted and experimentally observed IC₅₀ values. Thus, the generated models can be considered as interesting tools for the identification of novel smHDAC8 inhibitors.     

Prediction of the creep behaviour of polyethylene and molybdenum from stress relaxation experiments

In many applications it is useful to be able to convert observed creep data of a material to corresponding stress relaxation data or vice versa. If the material exhibits non-linear viscoelasticity such a conversion can be rather difficult. In this paper two semi-empirical flow equations, the power law and the exponential law, are used to convert stress relaxation data into corresponding creep behaviour data. These two flow equations are often used to describe non-linear viscoelastic behaviour. The procedure adopted here is based on the assumption that the creep data during the experiment decrease due to an increase in the internal stress level, thus decreasing the effective stress for flow. The conversion method is applied to high density polyethylene and polycrystalline molybdenum at room temperature. In general predictions using the power law are in better agreement with the experimental results than predictions using the exponential formula. The concepts of secondary and ceasing creep are discussed in terms of build-up of internal stress during the creep process.     

Modulated TiO2 nanotube stacks and their use in interference sensors

In the present work we control wall thickness oscillations in electrochemically grown TiO₂ nanotube arrays by defined water additions to an organic anodization electrolyte. Such corrugated TiO₂ nanotubes can be used to build optimized optical stacks that show under white light illumination well defined interference patterns which can be used as a self-cleaning platform for label-free sensing applications.     

A self-cleaning nonenzymatic glucose detection system based on titania nanotube arrays modified with platinum nanoparticles

In the present work, we show how TiO₂ nanotube layers that are decorated with a Pt-nanoparticle coating can be fabricated and operated as a reusable glucose sensing system. A critical amount of Pt coating is essential not only to provide an effective catalyst for glucose oxidation but also to establish a sufficient conductivity along TiO₂ nanotube walls to allow an efficient amperometric operation of the electrode. On such an electrode the self-cleaning photocatalytic features of TiO₂ can be maintained and used to re-establish poisoned activity of the Pt particles.     

A combinatorial proof of associativity of Ore extensions

We use a counting argument to show that Ore extensions are associative.     

Lithium-ion intercalation and electrochromism in ordered V2O5 nanoporous layers

Highly ordered V₂O₅ porous layers were fabricated from vanadium metal foils by self-organizing anodization. The defined porous structure of this material provides excellent lithium-ion transportation and intercalation/extraction properties. As a result the highly ordered porous structure shows a very good electrochromic performance with long term switching stability.