Validation of an empirical RNA-ligand scoring function for fast flexible docking using RiboDock®

We report the design and validation of a fast empirical function for scoring RNA-ligand interactions, and describe its implementation within RiboDock, a virtual screening system for automated flexible docking. Building on well-known protein-ligand scoring function foundations, features were added to describe the interactions of common RNA-binding functional groups that were not handled adequately by conventional terms, to disfavour non-complementary polar contacts, and to control non-specific charged interactions. The results of validation experiments against known structures of RNA-ligand complexes compare favourably with previously reported methods. Binding modes were well predicted in most cases and good discrimination was achieved between native and non-native ligands for each binding site, and between native and non-native binding sites for each ligand. Further evidence of the ability of the method to identify true RNA binders is provided by compound selection ('enrichment factor') experiments based around a series of HIV-1 TAR RNA-binding ligands. Significant enrichment in true binders was achieved amongst high scoring docking hits, even when selection was from a library of structurally related, positively charged molecules. Coupled with a semi-automated cavity detection algorithm for identification of putative ligand binding sites, also described here, the method is suitable for the screening of very large databases of molecules against RNA and RNA-protein interfaces, such as those presented by the bacterial ribosome.     

Two new standard reference materials for the determination of drugs of abuse in human hair

Two new standard reference materials (SRM) for drugs of abuse in human hair have been developed. SRM 2379 consists of hair spiked with cocaine, benzoylecgonine, cocaethylene, phencyclidine, amphetamine, and methamphetamine. SRM 2380 consists of hair spiked with codeine, morphine, monoacetylmorphine, and tetrahydrocannabinol (THC). The SRMs were prepared by soaking the hair in a solution of the target analytes in water-dimethylsulfoxide. The concentration of each analyte was determined using two methods, one based upon gas chromatography/mass spectrometry (GC/MS) and one based upon liquid chromatography/mass spectrometry (LC/MS). Both methods used 0.1 M HCl for extraction of all the analytes from the hair, except for THC, which was extracted with 1 M NaOH. For isolation of the analytes from the extracts, the GC/MS-based methods used different clean-up procedures from those used for the LC/MS-based methods. The results from the two methods were in good agreement with mean differences for the analytes ranging from 4% to 16%. These materials will enable laboratories performing analyses of hair for drugs of abuse to test the accuracy of their methods.     

Fluorous reverse-phase silica gel-supported Lewis acids as recyclable catalysts in water

Fluorous reverse-phase silica gel (FRPSG)-supported Lewis acids which have fluorous ligands acted as effective catalysts of Baeyer-Villiger and Diels-Alder reactions in water. Direct esterification of carboxylic acid with alcohol in organic media was also catalyzed. The FRPSG-supported Lewis acids could be recycled by simple filtration after the reaction.     

Large-volume PTV injection: Comparison of direct water injection and in-vial extraction for GC analysis of triazines

Summary The potential of large-volume PTV injection was studied for the analysis of triazine herbicides in water samples. Direct water injection and in-vial extraction were described and compared. Detection limits were between 0.01–0.02 μg L⁻¹ and relative standard deviations were <9%. Both methods are suitable for the analysis of triazines at ppt-level, although in-vial extraction is favourable for water samples with relatively large amounts of matrix components.     

The acidity functionsH 0 s of HCl solutions in EtOH with low water content

The acidity functionsH ₀ ^s of HCl solutions in EtOH-H₂O solvents containing 1.09, 3.0, and 5.0% water have been measured at 25 and 40 °C by the indicator method. The concentration of HCl changes from 10^–2 to 36m. Nitroanilines, for which a protonation mechanism is realized in the studied systems, were used as indicators.For each solvent,H ₀ ^s is temperature independent atm _HCl < 4, and acidity atm _HCl > 4 mol L^–1 increases more rapidly at 25 °C than at 40 °C. The acidity functions of aqueous and water-ethanol solutions of HCl were compared, and the concentrations of proton solvates of different compositions and their relative protonating ability were evaluated.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 1722–1725, October, 1994.This work was financially supported by the Russian Foundation for Basic Research (Project No. 93-03-18356).     

阴离子交换色谱-积分脉冲安培法测定鱼粉和玉米粉水解液中氨基酸

将高效阴离子交换色谱．积分脉冲安培直接检测法应用于鱼粉和玉米粉水解液中的氨基酸的分析测定。该方法使用Dionex AminoPac PA10阴离子交换柱为分析柱，控制柱温为35℃，以NaOH和NaAc的强碱性溶液为淋洗液，在合适的梯度条件下，可以实现对17种常见氨基酸的高效分离。在强碱性条件下，获得良好分离的各个氨基酸可在配有金工作电极的电化学检测器上以积分脉冲安培法获得高灵敏度的检测。在优化的测定条件下，该方法对这17种氨基酸的检出限在0．21—3．38pmol之间；峰面积校正曲线的线性范围为2—3个数量级；5次平行测定的峰面积的相对标准偏差RSD在0．32％—4．7％之间。该方法应用于玉米粉和鱼粉水解液中氨基酸含量的测定，结果良好。对玉米粉和鱼粉水解液标准加入的回收率分别在81．9％—108．0％和90．0％～108．0％之间。     

Development of B‐doped Si multiple delta‐layer reference materials for SIMS profiling

B‐doped Si multiple delta‐layers (MDL) were developed as certified reference materials (CRM) for secondary ion mass spectrometry (SIMS) depth profiling analysis. Two CRMs with different delta‐layer spacing were grown by ion beam sputter deposition (IBSD). The nominal spacing of the MDL for shallow junction analysis is 10 nm and that for high energy SIMS is 50 nm. The total thickness of the film was certified by high resolution transmission electron microscopy (HR‐TEM). The B‐doped Si MDLs can be used to evaluate SIMS depth resolution and to calibrate the depth scale. A consistency check of the calibration of stylus profilometers for measurement of sputter depth is another possible application. The crater depths measured by a stylus profilometer showed a good linear relationship with the thickness measured from SIMS profiling using the calibrated film thickness for depth scale calibration. The sputtering rate of the amorphous Si thin film grown by sputter deposition was found to be the same as that of the crystalline Si substrate, which means that the sputtering rate measured with these CRMs can be applied to a real analysis of crystalline Si. Copyright © 2005 John Wiley & Sons, Ltd.     

Infrared spectroscopic study of the interactions of nylon‐6 with water

We studied the interactions of nylon‐6 with water by following the Fourier transform infrared spectra of a hydrated thin film during dehydration. Very small changes in the spectra caused by the interactions were clearly revealed by the application of spectral subtraction. The water was found to interact with amide groups to form hydrogen bonds with non‐hydrogen‐bonded or free C?O and NH groups in the amorphous portion in the first hydration sphere. This was deduced from an analysis of minus and plus peaks appearing around the absorptions of the NH stretching, amide I band, and amide II bands in the difference spectra between the spectra during dehydration and the one at the most dehydration. The interactions of the amide groups with water were significantly stronger than the hydrogen bond between CO and NH in the crystalline portion, according to the magnitude of the frequency shift of relevant bands. Water, as the interacting counterpart, showed a distorted OH stretching absorption with two close peaks at about 3450 cm^?1. © 2003 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 41: 1722–1729, 2003     

Hydrate inclusion compounds

There are three general classes of hydrate inclusion compounds: the gas hydrates, the per-alkyl onium salt hydrates, and the alkylamine hydrates. The first are clathrates, the second are ionic inclusion compounds, the third are semi-clathrates. Crystallization occurs because the H₂O molecules, like SiO₂, can form three-dimensional four-connected nets. With water alone, these are the ices. In the inclusion hydrates, nets with larger voids are stabilized by including other guest molecules. Anions and hydrogen-bonding functional groups can replace water molecules in these nets, in which case the guest species are cations or hydrophobic moieties of organic molecules. The guest must satisfy two criteria. One is dimensional, to ensure a comfortable fit within the voids. The other is functional. The guest molecules cannot have either a single strong hydrogen-bonding group, such as an amide or a carboxylate, or a number of moderately strong hydrogen-bonding groups, as in a polyol or a carbohydrate.The common topological feature of these nets is the pentagonal dodecahedra: i.e., 5¹²-hedron. These are combined with 5¹²6²-hedra, 5¹²6³-hedra, 5¹²6⁴-hedra and combinations of these polyhedra, to from five known nets. Two of these are the well-known 12 and 17 Å cubic gas hydrate structures,Pm3n, Fd3m; one is tetragonal,P4 ₂/mnm, and two are hexagonal,P6 ₃/mmc andP6/mmm. The clathrate hydrates provide examples of the two cubic and the tetragonal structures. The alkyl onium salt hydrates have distorted versions of thePm3n cubic, the tetragonal, and one of the hexagonal structures. The alkylamine hydrate structures hitherto determined provide examples of distorted versions of the two hexagonal structures.There are also three hydrate inclusion structures, represented by single examples, which do not involve the 5¹²-hedra. These are 4(CH₃)₃CHNH₂·39H₂O which is a clathrate; HPF₆·6H₂O and (CH₃)₄NOH·5H₂O which are ionic-water inclusion hydrates. In the monoclinic 6(CH₃CH₂CH₂NH₂)·105H₂O and the orthorhombic 3(CH₂CH₂)₂NH·26H₂O, the water structure is more complex. The idealization of these nets in terms of the close-packing of semi-regular polyhedra becomes difficult and artificial. There is an approach towards the complexity of the water salt structures found in the crystals of proteins.