FIPSDock: A new molecular docking technique driven by fully informed swarm optimization algorithm

The accurate prediction of protein–ligand binding is of great importance for rational drug design. We present herein a novel docking algorithm called as FIPSDock, which implements a variant of the Fully Informed Particle Swarm (FIPS) optimization method and adopts the newly developed energy function of AutoDock 4.20 suite for solving flexible protein–ligand docking problems. The search ability and docking accuracy of FIPSDock were first evaluated by multiple cognate docking experiments. In a benchmarking test for 77 protein/ligand complex structures derived from GOLD benchmark set, FIPSDock has obtained a successful predicting rate of 93.5% and outperformed a few docking programs including particle swarm optimization (PSO)@AutoDock, SODOCK, AutoDock, DOCK, Glide, GOLD, FlexX, Surflex, and MolDock. More importantly, FIPSDock was evaluated against PSO@AutoDock, SODOCK, and AutoDock 4.20 suite by cross‐docking experiments of 74 protein–ligand complexes among eight protein targets (CDK2, ESR1, F2, MAPK14, MMP8, MMP13, PDE4B, and PDE5A) derived from Sutherland‐crossdock‐set. Remarkably, FIPSDock is superior to PSO@AutoDock, SODOCK, and AutoDock in seven out of eight cross‐docking experiments. The results reveal that FIPS algorithm might be more suitable than the conventional genetic algorithm‐based algorithms in dealing with highly flexible docking problems. © 2012 Wiley Periodicals, Inc.     

Temperature-sensitive membranes prepared from blends of poly(vinylidene fluoride) and poly(N-isopropylacrylamides) microgels

In this study, temperature-sensitive membranes were prepared by phase transition of the mixture of the temperature-sensitive poly(N-isopropylacrylamides) (PNIPAAM) microgels and poly(vinylidene fluoride). The results of Fourier transformed infrared spectrometer, X-ray photoelectron spectroscopy, elemental analysis, and scanning electron microscope photographs indicate that the PNIPAAM microgels are distributed more in the inner membrane than on the surface. The scanning electron microscope photographs reveal the blend membranes having porous surfaces with nanometer sizes and porous cross-sections with micrometer sizes. The addition of the PNIPAAM microgels is found to improve the porosity, the pore size, water flux, as well as to enhance the hydrophilicity and anti-fouling property of the blend membranes. The blend membrane shows temperature-sensitive permeability and protein rejection with the most dramatic change at around 32 °C which is the lower critical solution temperature of PNIPAAM, when water or bovine serum albumin solution flow through. Specifically, below 32 °C, the blend membrane shows a high protein rejection ratio which decreases with increasing temperature and a low water flux which increases with increasing temperature; above 32 °C, the blend membrane shows a low protein rejection ratio which decreases with increasing temperature and a high water flux which increases with increasing temperature.     

Buildup mechanism of carboxymethyl cellulose and chitosan self-assembled films

Films with different numbers of layers have been built by alternating the adsorption of carboxymethyl cellulose (CMC) and chitosan (CHI) at different pH levels. The adsorption process was recorded by quartz crystal microbalance (QCM). The results showed that under all pH conditions considered, the growth of the films is nonlinear. The film construction performed at pH 4.0 (preferred assembly pH) with different numbers of bilayers (CMC/CHI as one bilayer) was also observed step by step by atomic force microscopy (AFM). Comparing the growth process from QCM with the surface morphological changes from AFM shows the existence of an inhomogeneous structure for the first nine bilayers, and, after a coalescence of islands, an increase in the number of bilayers was demonstrated. The possible growth mechanism was also evaluated.     

Total synthesis of Daphnodorin A

A total synthesis of Daphnodorin A, a member of the Daphnodorins, was accomplished. Key features of the synthetic strategy include construction of 2-substituted-3-functionalized benzofuran via intramolecular Heck reaction and a mild Barton–McCombie deoxygenation process mediated by triethylborane. The total synthesis provided Daphnodorin A in 19.7% or 5.6% overall yield over 7 or 15 steps.     

Specific ion effects on the electrophoretic mobility of small,highly charged peptides: A modeling study

In this work, we use coarse‐grained modeling to study the free solution electrophoretic mobility of small highly charged peptides (lysine, arginine, and short oligos thereof (up to nonapeptides)) in NaCl and Na₂SO₄ aqueous solutions at neutral pH and room temperature. The experimental data are taken from the literature. A bead modeling methodology that treats the electrostatics at the level of the nonlinear Poisson Boltzmann equation developed previously in our laboratory is able to account for the mobility of all peptides in NaCl, but not Na₂SO₄. The peptide mobilities in Na₂SO₄ can be accounted for by including sulfate binding in the model and this is proposed as one possible explanation for the discrepancy. Oligo arginine peptides bind more sulfate than oligo lysines and sulfate binding increases with the oligo length.     

Ultra‐fast LC–ESI‐MS/MS method for the simultaneous determination of six highly toxic Aconitum alkaloids from Aconiti kusnezoffii radix in rat plasma and its application to a pharmacokinetic study

A fast, sensitive, and efficient ultra‐fast LC–ESI‐MS/MS method was developed for the simultaneous quantitation of six highly toxic Aconitum alkaloids, that is, aconitine, mesaconitine, hypaconitine, benzoylaconine, benzoylmesaconine, and benzoylhypaconine, in rat plasma after oral administration of crude ethanol extracts from Aconiti kusnezoffii radix by ultrasonic extraction, reflux extraction for 1 h, and reflux extraction for 3 h, respectively. The separation of six Aconitum alkaloids and aminopyrine (internal standard) was performed on an InertSustain® C₁₈ column, and the quantification of the analytes was performed on a 4000Q ultra‐fast LC–MS/MS system with turbo ion spray source in the positive ion and multiple‐reaction monitoring mode. Absolute recoveries ranged within 65.06–85.1% for plasma samples. The intra‐ and interday precision and accuracy of analytes were satisfactory. The methods were validated with sensitivity reaching the lower LOQ for aconitine, mesaconitine, hypaconitine, benzoylaconine, benzoylmesaconine, and benzoylhypaconine, which were 0.025, 0.025, 0.050, 0.025, 0.025, and 0.100 ng/mL, respectively. The method was successfully applied to a pharmacokinetic study of six Aconitum alkaloids in rat plasma after oral administration of crude ethanol extracts from the raw root of Aconitum kusnezoffii Reichb. by three different extraction processes.     

Determination of 12 potential nephrotoxicity biomarkers in rat serum and urine by liquid chromatography with mass spectrometry and its application to renal failure induced by Semen Strychni

In previous nephrotoxicity metabonomic studies, several potential biomarkers were found and evaluated. To investigate the relationship between the nephrotoxicity biomarkers and the therapeutic role of Radix Glycyrrhizae extract on Semen Strychni‐induced renal failure, 12 typical biomarkers are selected and a simple LC–MS method has been developed and validated. Citric acid, guanidinosuccinic acid, taurine, guanidinoacetic acid, uric acid, creatinine, hippuric acid, xanthurenic acid, kynurenic acid, 3‐indoxyl sulfate, indole‐3‐acetic acid, and phenaceturic acid were separated by a Phenomenex Luna C₁₈ column and a methanol/water (5 mM ammonium acetate) gradient program with a runtime of 20 min. The prepared calibration curves showed good linearity with regression coefficients all above 0.9913. The absolute recoveries of analytes from serum and urine were all more than 70.4%. With the developed method, analytes were successfully determined in serum and urine samples within 52 days. Results showed that guanidinosuccinic acid, guanidinoacetic acid, 3‐indoxyl sulfate, and indole‐3‐acetic acid (only in urine) were more sensitive than the conventional renal function markers in evaluating the therapeutic role of Radix Glycyrrhizae extract on Semen Strychni‐induced renal failure. The method could be further used in predicting and monitoring renal failure cause by other reasons in the following researches.     

Hydrothermal preparation of hybrid carbon/silica monolithic capillary column for liquid chromatography

A simple, easy and economical approach for the preparation of a hybrid carbon/silica monolithic capillary column was described for the first time by using silica monolith as framework in combination with hydrothermal carbonization at 180°C. During the preparation process, formamide was introduced to the reaction solutions to reduce the dissolution rate of monolithic silica skeleton and its optimal concentration was 1.5 M. Fourier transform infrared spectrometry, scanning electron microscopy, energy dispersive X‐ray spectrometry, and inverse size exclusion chromatography were carried out to characterize the as‐prepared column. The results demonstrated that carbon spheres ranging from 150 to 1000 nm were successfully attached to the surface of silica skeleton. The prepared hybrid carbon/silica column had a permeability of 4.4 × 10^?14 m². Chromatographic performance of the column was evaluated by separation of various compounds including alkylbenzenes, nucleosides and bases, and aromatic acids. The column exhibited an efficiency of 75 000 plates/m for butylbenzene at the optimal linear velocity of 0.23 mm/s. The successful separation of these compounds and the study on mechanism indicated that the column can be applied in mixed‐mode chromatography.     

Environmentally green approach to synthesize azo dyes based on 1-naphthol using nano BF3·SiO2 under solvent-free conditions

A series of azo dyes were efficiently synthesized by mixing aromatic amines and NaNO₂ in the presence of nano silica supported boron trifluoride (nano BF₃·SiO₂) and then diazo coupling with 1-naphthol under solvent-free conditions at room temperature. The present methodology has proven to be simple, rapid, environmentally benign, green, and cost-effective compared with previous synthetic methods. Also, by using this procedure, aryl diazonium salts supported on nano BF₃·SiO₂ were very stable to be kept at room temperature for several months without any special conditions.