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1.
Sean Ekins Alex M. Clark S. Joshua Swamidass Nadia Litterman Antony J. Williams 《Journal of computer-aided molecular design》2014,28(10):997-1008
Over the past decade we have seen a growth in the provision of chemistry data and cheminformatics tools as either free websites or software as a service commercial offerings. These have transformed how we find molecule-related data and use such tools in our research. There have also been efforts to improve collaboration between researchers either openly or through secure transactions using commercial tools. A major challenge in the future will be how such databases and software approaches handle larger amounts of data as it accumulates from high throughput screening and enables the user to draw insights, enable predictions and move projects forward. We now discuss how information from some drug discovery datasets can be made more accessible and how privacy of data should not overwhelm the desire to share it at an appropriate time with collaborators. We also discuss additional software tools that could be made available and provide our thoughts on the future of predictive drug discovery in this age of big data. We use some examples from our own research on neglected diseases, collaborations, mobile apps and algorithm development to illustrate these ideas. 相似文献
2.
The Future of Biological Mass Spectrometry 总被引:1,自引:0,他引:1
Vestal ML 《Journal of the American Society for Mass Spectrometry》2011,22(6):953-959
Biological applications of mass spectrometry have grown exponentially since the discovery of MALDI and electrospray ionization
techniques. This growth has been further fueled by the massive volume of DNA sequence information that is now available. An
ambitious goal of some of this research is to monitor the level and modification of all proteins and metabolites in a biological
sample such as plasma. A major research effort in mass spectrometry and related disciplines has been expended over the past
several years toward reaching this and other less ambitious goals, and considerable progress has been made; but the presently
available tools are clearly not sufficient for these very difficult tasks. In this “critical insight” discussion we suggest
that recent advances in time-of-flight (TOF) technology with MALDI ionization may provide some important new tools for achieving
the goals of biological research. 相似文献
3.
René Dybkaer 《Accreditation and quality assurance》2007,12(10):553-557
Laboratory medicine provides results for quantities as well as for properties having no magnitude. The terminology of the
latter is less well established and sources are contradictory. Two recent papers on “protometrology” published in this journal
offer an opportunity to discuss the necessary concept systems. The delineations of “metrology” versus “protometrology”, “observation”
versus “measurement”, and the generic division of “property” are examined with emphasis on avoiding conflict with the International
Vocabulary of Metrology. It is suggested that having “examination” as a top generic concept coupled with systematic modifiers
for division, especially ‘nominal’ and ‘ordinal’, is a preferable terminological solution.
相似文献
René Dybkaer |
4.
Effects of protein conformation in docking: improved pose prediction through protein pocket adaptation 总被引:2,自引:2,他引:0
Ajay N. Jain 《Journal of computer-aided molecular design》2009,23(6):355-374
Computational methods for docking ligands have been shown to be remarkably dependent on precise protein conformation, where
acceptable results in pose prediction have been generally possible only in the artificial case of re-docking a ligand into
a protein binding site whose conformation was determined in the presence of the same ligand (the “cognate” docking problem).
In such cases, on well curated protein/ligand complexes, accurate dockings can be returned as top-scoring over 75% of the
time using tools such as Surflex-Dock. A critical application of docking in modeling for lead optimization requires accurate
pose prediction for novel ligands, ranging from simple synthetic analogs to very different molecular scaffolds. Typical results
for widely used programs in the “cross-docking case” (making use of a single fixed protein conformation) have rates closer
to 20% success. By making use of protein conformations from multiple complexes, Surflex-Dock yields an average success rate
of 61% across eight pharmaceutically relevant targets. Following docking, protein pocket adaptation and rescoring identifies
single pose families that are correct an average of 67% of the time. Consideration of the best of two pose families (from alternate scoring regimes) yields a 75% mean success rate. 相似文献
5.
Summary An analytical evaluation of an HPLC method with diode array detection to separate and quantify polyphenolic compounds from
pears has been made. The method was applied to the quantitative analysis of phenolics from five pear horticultural cultivars
(“Agua”, “Blanquilla”, “Conference”, “Pasagrana” and “Decana”) in both peel and pulp matrices and evaluated for precision
and accuracy. Precision was taken as the reproducibility in peak area of the polyphenols of interest as well as in the slope
of calibration graphs. Values ranged 2–5%. Accuracy was evaluated by recovery of all polyphenolic compounds from both peel
and pulp in all pears investigated. Accuracy values ranged 92–102%, and were independent of the polyphenolic structure, horticultural
cultivar and matrix. Identification was by comparing retention times and UV spectra with those of standards when commercially
available. When not available commercially, provisional identification was according to spectral characteristics as well as
from isolation and hydrolysis data. Application of the method revealed differences between peel and pulp in all cases studied;
the higher levels of phenolics were found in the peels. “Decana” and “Pasagrana” cultivars showed the highest phenolic content
compounds whereas “Conference” showed the lowest. 相似文献
6.
Chemically Modified Carbon Nanotubes for Use in Electroanalysis 总被引:6,自引:0,他引:6
Gregory G. Wildgoose Craig E. Banks Henry C. Leventis Richard G. Compton 《Mikrochimica acta》2006,152(3-4):187-214
The discovery of carbon nanotubes has had a profound impact on many areas of science and technology, not least that of electroanalysis.
The properties and applications of carbon nanotubes themselves have been well reviewed in the literature and a number of reviews
with an electrochemical emphasis have been published. However, the modification of carbon nanotubes has recently been the
focus of much research, primarily to improve their solubility in various solvents. Yet modified carbon nanotube electrodes
also allow the electrochemist to tailor the properties of the carbon nanotubes, or the electrode surface to impart desired
properties such as enhanced sensing capabilities. In this review we attempt to comprehensively cover the different chemical
and electrochemical modification strategies and research carried out using modified carbon nanotubes for electroanalytical
and bioanalytical applications. Furthermore we also discuss the use of modified carbon nanotubes in electrocatalysis and biocatalysis
from an analytical aspect, as well as seeking to dispel some of the myths surrounding the “electrocatalytic” properties of
carbon nanotubes. 相似文献
7.
H. Oda M. Akiyama T. Masuda T. Nakamura 《Journal of Radioanalytical and Nuclear Chemistry》2007,272(2):439-442
We measured radiocarbon age of an ancient document “Minamoto no Yoritomo Sodehan Migyosho”. The content tells that it was
issued in 1189 by “Minamoto no Yoritomo” known as the virtually first shogun in Japan to grant “Matsugi” family the privilege
of controlling craftsmen of foundry industry. Paleographical views, however, suggested that it can be a counterfeit. The radiocarbon
dating clarified that the document was written not in the 12th but after the 16th century. 相似文献
8.
Singh N Chevé G Ferguson DM McCurdy CR 《Journal of computer-aided molecular design》2006,20(7-8):471-493
Combined ligand-based and target-based drug design approaches provide a synergistic advantage over either method individually. Therefore, we set out to develop a powerful virtual screening model to identify novel molecular scaffolds as potential leads for the human KOP (hKOP) receptor employing a combined approach. Utilizing a set of recently reported derivatives of salvinorin A, a structurally unique KOP receptor agonist, a pharmacophore model was developed that consisted of two hydrogen bond acceptor and three hydrophobic features. The model was cross-validated by randomizing the data using the CatScramble technique. Further validation was carried out using a test set that performed well in classifying active and inactive molecules correctly. Simultaneously, a bovine rhodopsin based “agonist-bound” hKOP receptor model was also generated. The model provided more accurate information about the putative binding site of salvinorin A based ligands. Several protein structure-checking programs were used to validate the model. In addition, this model was in agreement with the mutation experiments carried out on KOP receptor. The predictive ability of the model was evaluated by docking a set of known KOP receptor agonists into the active site of this model. The docked scores correlated reasonably well with experimental pK
i values. It is hypothesized that the integration of these two independently generated models would enable a swift and reliable identification of new lead compounds that could reduce time and cost of hit finding within the drug discovery and development process, particularly in the case of GPCRs.Electronic supplementary material Supplementary material is available in the online version of this article at and is accessible for authorized users. 相似文献
9.
10.
Vasil Simeonov Costel Sarbu Desire-Luc Massart Stefan Tsakovski 《Mikrochimica acta》2001,137(3-4):243-248
A data set (48×19) consisting of Danube river water analytical data collected at Galati site, Romania, during a four-year
period has been treated by principal components analysis (PCA). The PCA indicated that seven latent factors (“hardness”, “biochemical”,
“waste inlets”, “turbidity”, “acidity”, “soil extracts” and “organic wastes”) are responsible for the data structure and explain
over 80 % of the total variance of the system. Its complexity is further proved by the application of multiple linear regression
analysis on the absolute principal components scores (APCS) where the contribution of each natural or anthropogenic sources
in the factor formation is shown. The apportioning makes clear that each variable participates to a different extent to each
source and, in this way, no pure natural or pure anthropogenic influence could be determined. No specific seasonality for
the variables in consideration is found.
Received January 24, 2001. Revision July 6, 2001. 相似文献
11.
Chromatography: The separation technique of the 20th century 总被引:3,自引:0,他引:3
L. S. Ettre 《Chromatographia》2000,51(1-2):7-17
Summary M. S. Tswett contemplated the possibility of “chromatography” in 1899–1901 while carrying out his first research work on the
physico-chemical structure of plant chlorophylls, and he reported “on a new category of adsorption analysis” in 1903. The
evolution of chromatography followed the advances of this century: each decade brought new innovations based logically from
the previous one. By the end of the 20th Century chromatography has became the most widely used separation technique in chemistry
and biochemistry: thus, it is no exaggeration to call it the separation technique of the 20th Century. This paper investigates
the evolution of the various branches of chromatography.
An essential condition for all fruitful research is to have at one’s disposal a satisfactory technique. “Tout progrès scientific
est un progrès de méthode” as somebody once remarked. Unfortunately the methodology is frequently the weakest aspect of scientific
investigations. 相似文献
12.
E. -A. Uken P. Hahn-Weinheimer H. Stärk 《Journal of Radioanalytical and Nuclear Chemistry》1977,37(2):741-750
The three phases “dissolved solids”, “suspended solids” and “sediment” of four sampling sites along the river Isar were analysed
by INAA. In these as well as in the different grain-size fractions between<2 and 63 μm 17 trace elements were determined.
Compared with the values of other rivers in Middle Europe the river Isar is still below the levels of significant pollution. 相似文献
13.
Anthony P. Gies Anton Schotman David M. Hercules 《Analytical and bioanalytical chemistry》2010,396(4):1481-1490
In the present study, we address the possibility of matrix-assisted laser desorption/ionization (MALDI)–time-of-flight MS
analysis-induced chain fragmentation in poly(p-phenylene terephthalamide) (PPD-T) by considering two possible sources: (1) grinding-induced fragmentation resulting from
the evaporation–grinding MALDI sample preparation method (E-G method) and (2) in-source/metastable fragmentation induced by
the MALDI laser. An analysis of variance (ANOVA) statistical study found, with a high probability, that obtaining MALDI spectra
with the effective laser area as large as possible (the “fanned-out” setting) did not cause any chain fragmentation due to
the E-G MALDI sample preparation method, even when three additional grinding steps were used. However, the effect of laser
fluence was less clear. A significant effect of laser fluence was observed for lower mass oligomers (<1,400 Da), but there
was essentially no effect for higher mass species up to our limit of ANOVA measurement (∼2,300 Da). Plausible explanations
are presented to explain these observations. The most likely scenario is that “unexpected” end-group modifications occur during
PPD-T synthesis, producing small quantities of low mass species, which are amplified by the MALDI-EG extraction procedure. 相似文献
14.
F. Ditrói S. Takács F. Tárkányi E. Corniani R. W. Smith M. Jech T. Wopelka 《Journal of Radioanalytical and Nuclear Chemistry》2012,292(3):1147-1152
In the present work we demonstrate the development of a thin layer activation (TLA) method to be able to measure micrometer
wear or less by using radioactive tracing. In order to activate very swallow depths we decreased the bombarding energy to
the “linear” region of the cross-section curve. The disadvantage of the method is that the wear curve will be “linear” near
to the surface instead of “constant” as is the case with the usual (high energy) TLA. The advantage is that the activity of
the sample will be much lower and it is concentrated in the swallower studied depth. The other possible method is irradiation
under small angle (15 to 30° or even grazing incidence), which also causes a near-surface concentration of the activity produced.
Both methods are demonstrated with the most suitable nuclear reactions and some commonly used industrial materials. 相似文献
15.
V. V. Zhuikov 《Russian Journal of Electrochemistry》2000,36(2):117-127
Electrochemical reduction of organochlorosilanes and oxidation of hexaorganodisilanes may occur via dissociative and stepwise
mechanisms, the choice between which is determined by the balance between fundamental structural parameters of elementoorganic
molecules. The formation of radical anions of silyl-substituted chloromethane in the conditions of an electrochemical experiment
is shown. The formation is due to α-silicon stabilization of the intermediate during the electron transfer. The role of conjugation
and hyperconjugation in the organosilicon compounds’ reactivity is analyzed.
When employing terms “ stepwise ” and “ dissociative ” mechanisms of the electron transfer, we follow tradition introduced
and developed by J.-M. Saveant’s group [1] and recommended by the IUPAC Commission on Electrochemical Nomenclature [2]. The
terms refer to an electrochemically reversible transfer of electron whose kinetics does not limit the process rate as a whole
and to an electrochemically irreversible transfer which involves a bond cleavage in an elementary act of electron transfer.
The term “ activation ” mechanism, which is sometimes applied to electrochemically irreversible processes, is more universal;
however, it is somewhat not unique as compared with the term “ dissociative.” Coupled with “ associative,” the latter may
be used for indicating processes that involve the formation of a bond in an elementary act of electron transfer. 相似文献
16.
V. G. Granik S. S. Kiselev N. P. Solov'eva I. V. Persianova M. K. Polievktov Yu. N. Sheinker 《Chemistry of Heterocyclic Compounds》1980,16(3):256-260
The protonation of cyclic enamino ketones of the pyrrolidine, piperidine, and hexahydroazepine series, as well as their noncyclic
analogs, was studied by PMR spectroscopy. It is shown that the presence of a CH2 or CH3 group in the “enamine” position leads to C protonation (in CF3COOH). In the case of enamino ketones that do not contain substituents in the “enamine” α position N-and O-protonated forms
are observed in CF3COOH. The measured pKa values (in 10% alcohol) and the ΔpKa values (in nitromethane) of the enamino ketones show that the compounds for which C protonation is characteristic are two
to three orders of magnitude more basic than in the case of compounds that do not contain substituents in the “enamine” α
position; this is explained by the different character of protonation.
See [1] for communication 30.
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 344–348, March, 1980 相似文献
17.
Liquid crystalline(LC) polymers with a shish-kebab-type moiety on their cross-conjugated(p-phenylene)s-poly(p-phenylenevinylene) s main chains were synthesized through Gilch polymerization in order to develop a kind of polymers available for linearly polarized white-light-emitting from single chain.In this system,the 2,5-bis(4’-alkoxyphenyl)benzene as the "kebabs" connects with poly(p-phenylenevinylene)(PPV) main chain backbone using its molecular gravity center and the PPV as the "shish" or "skewer"(the "shish-kebab").The polymers possess desirable properties such as excellent solubility and liquid crystalline properties.To drop the "kebabs" of the 2,5-bis(4’-alkoxyphenyl)benzene into the orientation microgroove of aligned polyimide film,not only the "shish" of polymer main chain can be aligned by the virtue of orientation of "kebabs" but also the uniform cross-conjugated structure between the "kebabs" and "shish" can be broken. Then,the alignment of the polymer main chain showed yellow light emission and was also accompanied by orientation of the LC side chains showing blue light emission,this gave rise to a notable linearly polarized white fluorescence. 相似文献
18.
Multivariate analysis of HT/GC-(IT)MS chromatographic profiles of triacylglycerol for classification of olive oil varieties 总被引:1,自引:0,他引:1
Cristina Ruiz-Samblás Luis Cuadros-Rodríguez Antonio González-Casado Francisco de Paula Rodríguez García Paulina de la Mata-Espinosa Juan Manuel Bosque-Sendra 《Analytical and bioanalytical chemistry》2011,399(6):2093-2103
The ability of multivariate analysis methods such as hierarchical cluster analysis, principal component analysis and partial
least squares-discriminant analysis (PLS-DA) to achieve olive oil classification based on the olive fruit varieties from their
triacylglycerols profile, have been investigated. The variations in the raw chromatographic data sets of 56 olive oil samples
were studied by high-temperature gas chromatography with (ion trap) mass spectrometry detection. The olive oil samples were
of four different categories (“extra-virgin olive oil”, “virgin olive oil”, “olive oil” and “olive-pomace” oil), and for the
“extra-virgin” category, six different well-identified olive oil varieties (“hojiblanca”, “manzanilla”, “picual”, “cornicabra”,
“arbequina” and “frantoio”) and some blends of unidentified varieties. Moreover, by pre-processing methods of chemometric
(to linearise the response of the variables) such as peak-shifting, baseline (weighted least squares) and mean centering,
it was possible to improve the model and grouping between different varieties of olive oils. By using the first three principal
components, it was possible to account for 79.50% of the information on the original data. The fitted PLS-DA model succeeded
in classifying the samples. Correct classification rates were assessed by cross-validation. 相似文献
19.
Pavlina Simeonova Costel Sarbu Thomas Spanos Vasil Simeonov Stefan Tsakovski 《Central European Journal of Chemistry》2006,4(1):68-80
The present paper deals with the application of classical and fuzzy principal components analysis to a large data set from
coastal sediment analysis. Altogether 126 sampling sites from the Atlantic Coast of the USA are considered and at each site
16 chemical parameters are measured. It is found that four latent factors are responsible for the data structure (“natural”,
“anthropogenic”, “bioorganic”, and “organic anthropogenic”). Additionally, estimating the scatter plots for factor scores
revealed the similarity between the sampling sites. Geographical and urban factors are found to contribute to the sediment
chemical composition. It is shown that the use of fuzzy PCA helps for better data interpretation especially in case of outliers. 相似文献
20.
R. Padilla Alvarez E. Chinea Cano J. R. Estévez Alvarez E. D. Greaves 《Journal of Radioanalytical and Nuclear Chemistry》1999,240(2):517-522
“Cut-off” reflectors, which allow obtaining a reflected beam with almost no high energy radiation, as well as different monochromator
devices that reflect a beam of monoenergetic and polarized radiation are the most widely employed artifacts to perform the
excitation radiation improvement in analytical “non-expensive” TR spectrometers. The aim of this work consisted in testing
several monochromator devices: a multilayer structured mirror for soft X-rays (0.7–12.5 nm), as well as different bent and
flat crystals of wavelength dispersive spectrometers. The achieved instrumental detection limits for the selected monochromator
device are compared with the values obtained using a Suprasil Cut-off reflector and a C-W multilayer (d∼5 nm). Several human corporal fluid samples were analyzed to compare the spectral characteristics when using the Cut-Off
Reflector and the RAP flat crystal, respectively. 相似文献