Molecular similarity-based estimation of properties: a comparison of three structure spaces.

Similarity, like beauty, is an intuitive concept based on personal perception and bias. In the realm of molecular similarity, each method is user defined based on the features deemed important. A method's efficacy depends on the set of descriptors used to define the intermolecular similarity of chemicals and on the mathematical function used to quantify similarity.

Distance indices and their hyper-counterparts: intercorrelation and use in the structure-property modeling.

Intercorrelation between the Wiener index, hyper-Wiener index, Harary index, hyper-Harary index, detour index and hyper-detour index is studied on three sets of branched and unbranched alkanes and cycloalkanes with up to eight carbon atoms. First set (S-39) contains all alkanes from ethane to octane (39 molecules), the second set (S-139) 139 cyclic hydrocarbons from cyclopropane to branched and unbranched polycyclic octanes and the third set (S-178) is a combination of the first two sets (178 molecules). It is found that the pairs of distance indices and the corresponding hyper-counterparts are highly intercorrelated for all three sets.

A versatile in vivo footprinting technique using 1,10-phenanthroline-copper complex to study important cellular processes.

A number of reagents have been used to define the sequence-specific protein-DNA contacts by footprinting analysis. We report a new in vivo technique using the complex of 1,10-phenanthroline and copper [(OP(2))Cu] as a probe to study various intracellular DNA-protein interactions in whole cells. The versatility of the protocol is demonstrated by applying the technique to address various processes.

DNA unwinding mechanism for the transcriptional activation of momP1 promoter by the transactivator protein C of bacteriophage Mu.

Transcription factor-induced conformational changes in DNA are one of the mechanisms of transcription activation. C protein of bacteriophage Mu appears to transactivate the mom gene of the phage by this mode. DNA binding by C to its site leads to torsional changes that seem to compensate for a weak momP1 promoter having a suboptimal spacing of 19 bp between the poor -35 and -10 elements.

Methyl (SR)-10-chloro-1,2,3,4,5,6-hexahydro-6-hydroxy-8-methoxy-1-methyl-1,9-phenanthroline-6-carboxylate.

In the title compound, C(16)H(19)ClN(2)O(4), the pyridine ring is nearly planar, the piperidine ring is non-planar and the cyclohexane ring adopts a screw-boat conformation. The carboxylate group makes a dihedral angle of 80.9 (2) degrees with the least-squares plane through the cyclohexane ring.

Structural perturbation of proteins in low denaturant concentrations.

The presence of very low concentrations of the widely used chemical denaturants, guanidinium chloride and urea, induce changes in the tertiary structure of proteins. We have presented results on such changes in four structurally unrelated proteins to show that such structural perturbations are common irrespective of their origin. Data representative of such structural changes are shown for the monomeric globular proteins such as horseradish peroxidase (HRP) from a plant, human serum albumin (HSA) and prothrombin from ovine blood serum, and for the membrane-associated, worm-like elongated protein, spectrin, from ovine erythrocytes.

Power Doppler ultrasonography for the evaluation of skin tumors other than malignant melanoma.

The purpose of this prospective study was to evaluate the value of power Doppler ultrasonography (PDUS) in assessing the vascularity of skin tumors other than malignant melanoma, and to investigate possible diagnostic criteria to help to distinguish malignant from benign tumors preoperatively. Seventy-one patients with the clinical diagnosis of a skin tumor were initially evaluated by ultrasonography. Then PDUS was performed and the presence and type of vascularity (peripheral or mixed) were investigated.

Quantitative structure-property relationships (QSPRs) for the estimation of vapor pressure: a hierarchical approach using mathematical structural descriptors.

A set of 379 molecular descriptors was calculated for use in hierarchical quantitative structure-property relationship (QSPR) modeling of vapor pressure for a structurally diverse database consisting of 469 chemicals. The hierarchical approach utilizes topostructural, topochemical, geometrical, and quantum chemical descriptors in a stepwise fashion to develop QSPR models. In this way, the relative roles of the various levels of descriptors can be examined.

Interpretation of quantitative structure-property and -activity relationships.

The potential utility of data reduction methods (e.g. principal component analysis) for the analysis of matrices assembled from the related properties of large sets of compounds is discussed by reference to results obtained from solvent polarity scales, ongoing work on solubilities and sweetness properties, and proposed general treatments of toxicities and gas chromatographic retention indices.

Prediction of mutagenicity of aromatic and heteroaromatic amines from structure: a hierarchical QSAR approach.

Due to the lack of experimental data, there has been increasing use of theoretical structural descriptors in the hazard assessment of chemicals. We have used a hierarchical approach to develop class-specific quantitative structure-activity relationship (QSAR) models for the prediction of mutagenicity of a set of 95 aromatic and heteroaromatic amines. The hierarchical approach begins with the simplest molecular descriptors, the topostructural, which encode limited chemical information.

QSAR with few compounds and many features.

Fitting quantitative structure-activity relationships (QSAR) requires different statistical methodologies and, to some degree, philosophies depending on the "shape" of the data matrix. When few features are used and there are many compounds, it is a reasonable expectation that good feature subset selection may be made and that nonlinearities and nonadditivities can be detected and diagnosed. Where there are many features and few compounds, this is unrealistic.

A new descriptor for structure-property and structure-activity correlations.

We consider an improvement of a multiple regression analysis (MRA) for the correlation of boiling points of alcohols using descriptors that involve a variable part. In the search for the best descriptors based on weighted paths we came upon a novel molecular descriptor, the use of which was apparently overlooked in the past. The novel descriptor counts paths of length three; however, only those associated with an oxygen atom are counted.

On the characterization of DNA primary sequences by triplet of nucleic acid bases.

We consider construction of a set of smaller 4 x 4 matrices to represent DNA primary sequences which are based on enumeration of all 64 triplets of nucleic acids bases. The leading eigenvalue from the constructed matrices has been selected as an invariant for construction of a vector to characterize DNA. Additional invariants considered of the derived condensed matrices of DNA include a 64-component vector, the components of which consist of ordered triplets XYZ, with X, Y, Z = A, C, G, T.

On use of the variable connectivity index 1chi(f) in QSAR: toxicity of aliphatic ethers.

The number of non-hydrogen atoms in a molecule, N, appears as a very good molecular descriptor for the toxicity of aliphatic ethers, despite the fact that it does not differentiate among isomers. The regression based on N as a descriptor for the toxicity in mice of 21 alkyl ethers was reported to yield the regression coefficient r = 0.9751.

On structural interpretation of several distance related topological indices.

We consider the role that individual bonds play in bond-additivities in order to better understand the structural basis of various topological indices. In particular we consider indices closely related to the Wiener index (W) and the distance matrix and search for optimal weights of terminal and interior CC bonds in alkanes for a selection of physicochemical properties. It is interesting to note that different properties are associated with different relative roles of the exterior and the interior CC bonds.

Characterization of DNA primary sequences based on the average distances between bases.

We outline numerical characterization of DNA primary sequence based on calculation of the average distance between pairs of nucleic acid bases. This leads to a representation of DNA by a condensed 4 x 4 symmetrical matrix, the elements of which give the average separation between pair of bases X, Y in DNA (X, Y = A, C, G, T). As an invariant of choice we consider the leading eigenvalue of the derived 4 x 4 matrix.

Comparison of a neural net-based QSAR algorithm (PCANN) with Hologram- and multiple linear regression-based QSAR approaches: application to 1,4-dihydropyridine-based calcium channel antagonists.

A QSAR algorithm (PCANN) has been developed and applied to a set of calcium channel blockers which are of special interest because of their role in cardiac disease and also because many of them interact with P-glycoprotein, a membrane protein associated with multidrug resistance to anticancer agents. A database of 46 1,4-dihydropyridines with known Ca2+ channel binding affinities was employed for the present analysis. The QSAR algorithm can be summarized as follows: (1) a set of 90 graph theoretic and information theoretic descriptors representing various structural and topological characteristics was calculated for each of the 1,4-dihydropyridines and (2) principal component analysis (PCA) was used to compress these 90 into the eight best orthogonal composite descriptors for the database.

Effect of osmolytes and chaperone-like action of P-protein on folding of nucleocapsid protein of Chandipura virus.

Amino acid sequences of nucleocapsid proteins are mostly conserved among different rhabdoviruses. The protein plays a common functional role in different RNA viruses by enwrapping the viral genomic RNA in an RNase-resistant form. Upon expression of the nucleocapsid protein alone in COS cells and in bacteria, it forms large insoluble aggregates.

Molecular similarity based estimation of properties: a comparison of structure spaces and property spaces.

Molecular similarity methods have emerged as powerful tools in analog selection, chemical classification based on toxic modes of action, and property estimation. The basic assumption of structure-activity relationships (SAR) is that similar structures usually have similar properties. Therefore, similarity methods can be used for the selection of analogs and estimation of properties of chemicals from their structural analogs in property spaces.

Intrinsic DNA distortion of the bacteriophage Mu momP1 promoter is a negative regulator of its transcription. A novel mode of regulation of toxic gene expression.

The momP1 promoter of the bacteriophage Mu mom operon is an example of a weak promoter. It contains a 19-base pair suboptimal spacer between the -35 (ACCACA) and -10 (TAGAAT) hexamers. Escherichia coli RNA polymerase is unable to bind to momP1 on its own.

Effect of cholesterol on interaction of dibucaine with phospholipid vesicles: a fluorescence study.

Interaction of the local anesthetic dibucaine with small unilamellar vesicles of dimyristoylphosphatidylcholine (DMPC) and dioleoyl phosphatidylcholine (DOPC) containing different mol percents of cholesterol has been studied by fluorescence spectroscopy. Fluorescence measurements on dibucaine in presence of phospholipid vesicles containing various amounts of cholesterol yielded a pattern of variation of wavelength at emission maximum and steady-state anisotropy which indicated that the microenvironment of dibucaine is more polar and flexible in membranes that contain cholesterol than in membranes without cholesterol. Experiments on quenching of fluorescence from membrane-associated dibucaine by potassium iodide showed a marked increase in quenching efficiency as the cholesterol content of the vesicles was increased, demonstrating increased accessibility of the iodide quenchers to dibucaine in the presence of cholesterol, when compared to that in its absence.

Unilateral pellucid marginal degeneration.

Pellucid marginal degeneration (PMD) is a rare and usually a bilateral condition. We report a case of typical PMD with a unilateral presentation.

Inhibition of Mycobacterium smegmatis topoisomerase I by specific oligonucleotides.

DNA topoisomerase I from Mycobacterium smegmatis unlike many other type I topoisomerases is a site specific DNA binding protein. We have investigated the sequence specific DNA binding characteristics of the enzyme using specific oligonucleotides of varied length. DNA binding, oligonucleotide competition and covalent complex assays show that the substrate length requirement for interaction is much longer ( approximately 20 nucleotides) in contrast to short length substrates (eight nucleotides) reported for Escherichia coli topoisomerase I and III.

On 3-D graphical representation of DNA primary sequences and their numerical characterization.

In this article we (1) outline the construction of a 3-D "graphical" representation of DNA primary sequences, illustrated on a portion of the human beta globin gene; (2) describe a particular scheme that transforms the above 3-D spatial representation of DNA into a numerical matrix representation; (3) illustrate construction of matrix invariants for DNA sequences; and (4) suggest a data reduction based on statistical analysis of matrix invariants generated for DNA. Each of the four contributions represents a novel development that we hope will facilitate comparative studies of DNA and open new directions for representation and characterization of DNA primary sequences.

Assessment of some important anatomical variations and dangerous areas of the paranasal sinuses by computed tomography in children.

The purpose of this study is to determine important variations and areas of risk for major complications in paranasal computed tomography (CT). We also made specific measurements for individual differences. This study consisted of 64 children (128 sides).