The presentation of chemical data collections including the precision

Summary Generally the discussion of analytical results of a population is restricted to the calculation of an overall mean and standard deviation. In this paper a method is described enabling the direct incorporation of peculiarities in the distribution of the individual values avoiding the loss of information. The peculiarities mentioned are variations in precision from day to day or even within one day. Presenting the whole analysed population including precision gives a clear graphic representation of this population. The required computer programs are given in outline.

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Darstellung chemischer Datensammlungen einschließlich der Präzision

Zusammenfassung Im allgemeinen ist die Diskussion einer Datensammlung auf die Berechnung des Gesamt-Mittelwertes und der Standardabweichung beschränkt. Eine Methode wird daher beschrieben, die es erlaubt, Besonderheiten direkt in die Verteilung der individuellen Werte einzubeziehen, ohne daß ein Verlust an Information eintritt. Diese Besonderheiten beziehen sich auf Veränderungen der Präzision von Tag zu Tag oder selbst innerhalb eines Tages. Es ergibt sich eine klare graphische Darstellung der gesamten Datensammlung. Die erforderlichen Computerprogramme werden beschrieben.

     

A data base of data banks for toxicological information

The procedures necessary to find the appropriate data banks in seeking particular information or data are much less systematic than the way in which the information is stored at some data banks. Based on the information taken from several hundred direct-mailed questionnaires, a conceptual design is proposed for a data base of toxicological data banks relating to other areas such as medicine, pharmacology, biology, chemistry and environmental science. The system (not yet implemented) contains nearly 150 data banks (both computerized and manual) all over the world with data on the type of information, the way to obtain it, its cost, etc.     

Computation of the physio-chemical properties and data mining of large molecular collections

Very large data sets of molecules screened against a broad range of targets have become available due to the advent of combinatorial chemistry. This information has led to the realization that ADME (absorption, distribution, metabolism, and excretion) and toxicity issues are important to consider prior to library synthesis. Furthermore, these large data sets provide a unique and important source of information regarding what types of molecular shapes may interact with specific receptor or target classes. Thus, the requirement for rapid and accurate data mining tools became paramount. To address these issues Pharmacopeia, Inc. formed a computational research group, The Center for Informatics and Drug Discovery (CIDD).* In this review we cover the work done by this group to address both in silico ADME modeling and data mining issues faced by Pharmacopeia because of the availability of a large and diverse collection (over 6 million discrete compounds) of drug-like molecules. In particular, in the data mining arena we discuss rapid docking tools and how we employ them, and we describe a novel data mining tool based on a ID representation of a molecule followed by a molecular sequence alignment step. For the ADME area we discuss the development and application of absorption, blood-brain barrier (BBB) and solubility models. Finally, we summarize the impact the tools and approaches might have on the drug discovery process.     

Reduction of the virtual space for coupled-cluster excitation energies of large molecules and embedded systems

We investigate how the reduction of the virtual space affects coupled-cluster excitation energies at the approximate singles and doubles coupled-cluster level (CC2). In this reduced-virtual-space (RVS) approach, all virtual orbitals above a certain energy threshold are omitted in the correlation calculation. The effects of the RVS approach are assessed by calculations on the two lowest excitation energies of 11 biochromophores using different sizes of the virtual space. Our set of biochromophores consists of common model systems for the chromophores of the photoactive yellow protein, the green fluorescent protein, and rhodopsin. The RVS calculations show that most of the high-lying virtual orbitals can be neglected without significantly affecting the accuracy of the obtained excitation energies. Omitting all virtual orbitals above 50 eV in the correlation calculation introduces errors in the excitation energies that are smaller than 0.1 eV. By using a RVS energy threshold of 50 eV, the CC2 calculations using triple-ζ basis sets (TZVP) on protonated Schiff base retinal are accelerated by a factor of 6. We demonstrate the applicability of the RVS approach by performing CC2/TZVP calculations on the lowest singlet excitation energy of a rhodopsin model consisting of 165 atoms using RVS thresholds between 20 eV and 120 eV. The calculations on the rhodopsin model show that the RVS errors determined in the gas-phase are a very good approximation to the RVS errors in the protein environment. The RVS approach thus renders purely quantum mechanical treatments of chromophores in protein environments feasible and offers an ab initio alternative to quantum mechanics/molecular mechanics separation schemes.     

A performance criterion for information theoretic data analysis

A previously unobserved electronic state in fluorobenzene appears as a two-photon resonance in the multiphoton resonance ionization spectrum. The band system is assigned to the 3s Rydberg ← b₂(π) HOMO transition with a quantum defect of 0.83 and an origin at 50 914 ± 15 cm^?1. Its correspondence to the benzene state characterized by Johnson in the same region assigns that state to E_1g 3s Rydberg.     

Exploiting scale-free information from expression data for cancer classification

Most studies concerning expression data analyses usually exploit information on the variability of gene intensity across samples. This information is sensitive to initial data processing, which affects the final conclusions. However expression data contains scale-free information, which is directly comparable between different samples. We propose to use the pairwise ratio of gene expression values rather than their absolute intensities for a classification of expression data. This information is stable to data processing and thus more attractive for classification analyses. In proposed schema of data analyses only information on relative gene expression levels in each sample is exploited. Testing on publicly available datasets leads to superior classification results.     

Mutual information and electron correlation in momentum space

Mutual information and information entropies in momentum space are proposed as measures of the nonlocal aspects of information. Singlet and triplet state members of the helium isoelectronic series are employed to examine Coulomb and Fermi correlations, and their manifestations, in both the position and momentum space mutual information measures. The triplet state measures exemplify that the magnitude of the spatial correlations relative to the momentum correlations depends on and may be controlled by the strength of the electronic correlation. The examination of one- and two-electron Shannon entropies in the triplet state series yields a crossover point, which is characterized by a localized momentum density. The mutual information density in momentum space illustrates that this localization is accompanied by strong correlation at small values of p.     

An information theoretical evaluation of the applicability of the ASTM infrared data base for retrieval purposes

Summary The information content of the identification by retrieval with binary coded infrared spectra (ASTM infrared datafile), taking into account the correlations between the speaks and the errors in the coded spectra, amounts to about 21 bits. This amount of information can be obtained when use is made of not more than 93 wavelength intervals, selected from the total number of 140 intervals that are available for retrieval. The information content can be raised to about 29 bits when for the retrieval procedure a window of 0.3 is introduced, thereby requiring only 72 intervals. The influence of the composition of the dataset upon the information content is considerable; for hydrocarbons an amount of information of only 15 bits is obtained with a search using 79 intervals.The probability of the match between the spectrum of the unknown compound and the right reference spectrum being superior to all other possible matches will increase from virtually zero to about 88% when a window of 0.3 is used.

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Eine informationstheoretische Auswertung der Anwendung der ASTM-Sammlung — Infrarotspektren für die Bibliothekssuche

Zusammenfassung Der Informationsgehalt für die Identifizierung durch Vergleich binÄr codierter Infrarotspektren (ASTM-Sammlung Infrarotspektren) betrÄgt unter Berücksichtigung der Ungenauigkeiten und der Korrelation zwischen den Banden etwa 21 Bits. Diese Informationsmenge kann erhalten werden aus dem Vergleich von nur 93 WellenlÄngen-Intervallen, die aus einer Gesamtzahl von 140 verfügbaren selektiert wurden.Der Informationsgehalt für die Bibliothekssuche kann bis zu 29 Bits zunehmen, wenn für die Suche ein Fenster von 0,3 angewendet wird; die Zahl der benötigten Intervalle betrÄgt dann nur 72. Aus verschiedenen Spektrensammlungen erhÄlt man verschiedene Informationsmengen; zum Beispiel betrÄgt der Informationsgehalt für Kohlenwasserstoffe nur 15 Bits unter Benutzung von 79 Intervallen. Die Wahrscheinlichkeit, da\ der Vergleich des Spektrums einer unbekannten Verbindung mit dem richtigen Vergleichsspektrum eine bessere übereinstimmung liefert als der Vergleich mit allen anderen Vergleichsspektren, nimmt von ungefÄhr null bis 88% zu, wenn ein Fenster von 0,3 angewendet wird.

     

Reduction of biselenites into polyselenides in interlayer space of layered double hydroxides

A selenous acid (H₂SeO₃) precursor was intercalated as biselenite (HSeO₃⁻) ions into the interlayer gallery of carbonated magnesium aluminum layered double hydroxide (MgAl-LDH) in aqueous solution. Reduction reaction of selenous ions by aqueous hydrazine solution produced polyselenide intercalated LDHs which were consecutively exchanged with iodide through redox reaction under iodine vapor. The polyselenide containing LDHs adsorbed iodine vapor spontaneously and triiodide was incorporated in the interlayer space followed by formation of selenium polycrystalline phase. Two dimensional framework of MgAl-LDH is strong enough to resist against the reducing power of hydrazine as well as oxidation condition of iodine. The SEM data demonstrated that the shapes of LDH polycrystalline have little changed after the above redox reactions. The polyselenide and iodide LDH products were analyzed by XRD, Infrared and Raman spectra which strongly suggested the horizontal arrangement of polyselenide and triiodide in gallery space of LDHs.     

Gamma irradiation of protein-based textiles for historical collections decontamination

In order to investigate the effect of gamma rays on cultural heritage materials, samples of silk and wool fabrics were subjected to accelerated ageing testing and then irradiated with different gamma-ray doses: 10 and 25 kGy. In the data analysis, combining thermal analysis (TG and DTG), infrared spectroscopy (FTIR-ATR) and mechanical tests allowed us to explore the changes in physical and chemical features for silk and wool, in relationship to the radiation doses. This analytical protocol offers a way to examine the behaviour of the textiles made of wool and silk within museum collections and their response to gamma-rays irradiation treatment. An exposure to a dose of 10 kGy did not cause significant changes in the tested properties; however, higher doses initiated irreversible loss in the physical and chemical stability of protein-based fabrics. Increasing the irradiation dose above 10 kGy has drastic effects in the loss of elasticity and the mechanical resistance of the tested yarns.     

Geometrical bounding of data space and nonlinear classification of chemical data using MPGA algorithm

This paper develops a multi-parturition genetic algorithm (MPGA) to be used in geometrical bounding of the overlapped clusters in a data set for the classification of chemical data. Two new operators have been introduced to modify the conventional genetic algorithm, namely, multi-parturition and decimation and orientated creation to improve the linear classification results and diminish the computational time. To circumvent the difficulty commonly encountered in the treatment of linearly inseparable chemical data sets, the optimized linear classifier is further modified to provide a complementary nonlinear classifier. For this reason the space regions of the overlapped clusters have been bounded by erection of half-hyperellipsoids over the linearly misclassified patterns. The proposed MPGA was applied to classify a number of chemical and other data sets with a dimension from 4 to 14. Experimental results have indicated that the proposed MPGA could classify seriously overlapped data sets with an acceptable error rate.     

Estimation of the size of drug-like chemical space based on GDB-17 data

The goal of this paper is to estimate the number of realistic drug-like molecules which could ever be synthesized. Unlike previous studies based on exhaustive enumeration of molecular graphs or on combinatorial enumeration preselected fragments, we used results of constrained graphs enumeration by Reymond to establish a correlation between the number of generated structures (M) and the number of heavy atoms (N): logM = 0.584 × N × logN + 0.356. The number of atoms limiting drug-like chemical space of molecules which follow Lipinsky’s rules (N = 36) has been obtained from the analysis of the PubChem database. This results in M ≈ 10³³ which is in between the numbers estimated by Ertl (10²³) and by Bohacek (10⁶⁰).     

Real space functions from experimental small angle scattering data

A model free evaluation of small angle scattering data of interacting particles results in real space curves that are often difficult to interpret. It is then easier to use a model for the inter and/or the intra particle effects. Such a procedure requires the selection of appropriate models. The selection of the correct model is facilitated by interpreting parts of the purely model free real space results of the scattering data. The corresponding functions for hard, charged, and attractive spheres are simulated as well as the curves of spheres in BCC crystalline order and of cylinders in hexagonal order. The simulated results are compared to experimental data obtained from concentrated emulsions. Estimations for particle diameter, type of interaction, next neighbour distance, and volume fraction can be deduced from most of the data.     

Microcomputer mass-spectral information system with categorized data bases

Twelve special-purpose mass spectral data bases (MIMS-i) containing data on alkaloids, organometallic compounds, steroids, amino acids, etc., were established on an IBM-PC/XT microcomputer. A retrieval system incorporating different query and search methods was built for these data bases. The structures and methods used in the establishment of the data bases, some special search procedures and the capability of the system are discussed.     

Controlling the transmission of stereochemical information through space in terphenyl-edged Fe4L6 cages

A series of terphenyl-edged Fe(4)L(6) cages were synthesized from substituted 4,4'-diamino-p-terphenyls, 2-formylpyridine, and iron(II). For the parent diaminoterphenyl, all three possible diastereomers, with T, S(4), and C(3) point symmetries, were formed in nearly equal amounts, as determined by (1)H and (13)C NMR. When 2,2″-dimethylterphenylenediamine was used, the T-symmetry diastereomer was observed to predominate. The use of 2',3',5',6'-tetramethylterphenylenediamine generated predominantly the S(4) cage diastereomer, whereas 2',5'-dimethylterphenylenediamine produced the C(3)-symmetric cage to a greater degree than the other two diastereomers. The factors contributing to the transfer of chiral information between metal vertices were analyzed, and the general principles underlying the delicately balanced thermodynamics were determined.