Biomedical subjects

S C Basak

Publications and source records attributed to S C Basak.

At least 19 recordsLinked to original sources

PubMed2006

Differential display analysis of gene expression in two immunologically distinct strains of Eimeria maxima.

Gene expression during sporulation and sporozoite excystation of two strains of Eimeria maxima was analyzed using the mRNA differential display technique. The two strains, the Guelph strain (GS) and a single sporocyst-derived strain (M6) from Florida, have been shown to be immunologically distinct. We isolated and cloned a 453-bp complimentary DNA (cDNA) fragment (GS-453) found only in GS sporozoites. In GS, this mRNA begins to be expressed during the earliest stages of oocyst sporulation and is continuously expressed up to and including in the excysted sporozoite. In all Northern blots, digoxigenin (DIG)-labeled GS-453 probe recognized an mRNA of approximately 1.6 kb from GS but not from RNA of M6. Southern blots using various endonucleases and probed with DIG-labeled GS-453 demonstrated that the genomes of both strains contained sufficiently similar sequences to permit hybridization with the probe, but the pattern of hybridization differed between the two strains. Extensive searches of the GenBank, European Molecular Biology Laboratory, and various apicomplexan expressed sequence tag databases using the DNA or inferred amino acid sequences of GS-453 cDNA clone did not identify similarity to any existing sequences.

Animals↗

PubMed2006

Complexity of chemical graphs in terms of size, branching, and cyclicity.

Chemical graph complexity depends on many factors, but the main ones are size, branching, and cyclicity. Some molecular descriptors embrace together all these three parameters, which cannot then be disentangled. The topological index J (and its refinements that include accounting for bond multiplicity and the presence of heteroatoms) was designed to compensate in a significant measure for graph size and cyclicity, and therefore it contains information mainly on branching. In order to separate these factors, two new indices (F and G) related with J are proposed, which allow to group together graphs with the same size into families of constitutional formulas differing in their branching and cyclicity. A comparison with other topological indices revealed that a few other topological indices vary similarly with index G, notably DN2S4 among the triplet indices, and TOTOP among the indices contained in the Molconn-Z program. This comparison involved all possible chemical graphs (i.e. connected planar graphs with vertex degrees not higher than four) with four through six vertices, and all possible alkanes with four through nine carbon atoms.

Alcohols↗

PubMed2006

Prediction of tissue: air partition coefficients--theoretical vs. experimental methods.

Predictive QSAR models for rat and human tissue : air partition coefficients, namely blood : air, fat : air, brain : air, liver : air, muscle : air, and kidney : air were developed utilizing experimentally determined partition coefficients for 131 chemicals obtained from the literature and molecular descriptors based solely on chemical structure. The descriptors were partitioned into four hierarchical classes, including topostructural, topochemical, 3-dimensional, and ab initio quantum chemical. Three types of regression methodologies--ridge regression, principal components regression, and partial least squares regression--were used comparatively in the development of the structure-based models. In addition to the structure-based models, ordinary least squares regression was used to develop comparative models based on experimentally determined properties including saline : air and olive oil : air partition coefficients. The results of the study indicate that many of the structure-based models are comparable or superior to their respective property-based models. This is an important result considering that structural descriptors can be calculated quickly and inexpensively for both existing chemicals and those not yet synthesized. It was also found that ridge regression outperformed principal components regression and partial least squares regression, with respect to the structure-based models, and that generally the topochemical descriptors alone produced models of good predictive ability.

Air Pollutants↗

PubMed2006

Optimal neighbor selection in molecular similarity: comparison of arbitrary versus tailored prediction spaces.

Three classes of arbitrary quantitative molecular similarity analysis (QMSA) methods have been computed using atom pairs (APs), topological indices (TIs), and principal components (PCs) derived from topological indices. Tailored QMSA models have been developed from TIs selected through ridge regression. K-nearest neighbor (kNN) based estimation has been applied to all of the methods to estimate normal vapor pressure (p(vap)) and water solubility (sol) for a set of 194 chemicals. Results show that the tailored QMSA methods are superior to arbitrary similarity methods in estimating both of these properties for the given set of chemicals.

Hydrocarbons↗

PubMed2005

Quantitative structure-activity relationship modeling of insect juvenile hormone activity of 2,4-dienoates using computed molecular descriptors.

Juvenile hormone (JH) activity of one hundred and eighty 2,4-dienoates reported for the larvae/pupae of six insect species was modeled using 915 atom pairs and 258 global molecular descriptors (topological and geometrical). Ridge regression, principal component regression and partial least square regression methods were used to model each of the JH activities. The use of all of the available parameters did not yield any good models, and extensive predictor trimming was necessary to improve the models. Ridge regression was found to give the best results among the three statistical tools used. The top ten molecular descriptors selected based on the t-statistic for each of the six models were found to be mostly atom pairs containing heteroatoms and topochemical descriptors. This suggests the importance of the chemical nature of the ligand rather than mere space-filling as the basis of the JH bioactivity. The residual plots indicate the existence of some non-linear relations, and recursive partitioning was used to capture any nonlinear relation between the bioassays and the molecular descriptors.

Alkenes↗

PubMed2002

Prediction of tissue-air partition coefficients: a comparison of structure-based and property-based methods.

Three linear regression methods were used to develop models for the prediction of rat tissue-air partition coefficient (P). In general, ridge regression (RR) was found to be superior to principal component regression (PCR) and partial least squares regression (PLS). A set of 46 diverse low molecular-weight volatile chemicals was used to model fat-air, liver-air and muscle-air partition coefficients for male Fischer 344 rats. Comparisons were made between models developed using descriptors based solely on molecular structure and those developed using experimental properties, including saline-air and olive oil-air partition coefficients, as independent variables, indicating that the structure-property correlations are comparable to the property-property correlations. Multiple structure-based models were developed utilizing various classes of structural descriptors based on level of complexity, i.e. topostructural (TS), topochemical (TC), 3-dimensional (3D) and calculated octanol-water partition coefficient. In most cases, the structure-based models developed using only the TC descriptors were found to be superior to those developed using other structural descriptor classes. Haloalkane subgroups were modeled separately for comparative purposes, and although models based on the congeneric compounds were superior, the models developed on the complete sets of diverse compounds were acceptable. Comparisons were also made with respect to the types of descriptors important for partitioning across the various media.

Air↗

PubMed2002

Novel matrix invariants for characterization of changes of proteomics maps.

Previous studies on mathematical characterization of proteomics maps by sets of map invariants were based on the construction of a set of distance-related matrices obtained by matrix multiplication of a single matrix by itself. Here we consider an alternative characterization of proteomics maps based on a set of matrices characterizing local features of an embedded zigzag curve over the map. It is shown that novel invariants can well characterize proteomics maps. Advantages of the novel approach are discussed.

Models, Theoretical↗

PubMed2002

Quantitative molecular similarity analysis (QMSA) methods for property estimation: a comparison of property-based, arbitrary, and tailored similarity spaces.

Three classes of arbitrary quantitative molecular similarity analysis (QMSA) methods have been computed using atom pairs, topological indices, and physicochemical properties. Tailored QMSA models have been developed using a selected number of TIs chosen by ridge regression. The methods have been applied to the K-nearest neighbor based estimation of log P of two sets of chemicals. Results show that the property-based and tailored QMSA methods are superior to the arbitrary similarity methods in estimating log P of both sets of chemicals

Chemical Phenomena↗

PubMed2002

Structure-water solubility modeling of aliphatic alcohols using the weighted path numbers.

The structure-water solubility modeling of aliphatic alcohols was performed using the weighted path numbers. Aliphatic alcohols were represented by weighted trees. The weight of the edge representing C-O bond was taken to be x, while the weights of C-C bonds were taken to be all equal to one. Four (one-, two-, three- and four-descriptor) models with weighted path numbers were considered. They were compared with models based on surface areas of aliphatic alcohols, models based on the vertex-connectivity indices for the corresponding alkanes, models based on orthogonal valence vertex-connectivity indices, models based on valence vertex- and edge-connectivity indices with optimum exponents and models based on weighted line graphs. The main result of this comparative study is that the models based on two, three, or four weighted path numbers posses the best statistical characteristics of all models considered in this paper. In addition, the predictive performance of these models was also tested using the training/test set partition. Very good and stable predictions for 19 test set compounds were obtained. For this data set we find, in all performed tests of models, that optimum x values are in the range 3.0-4.0. This result supports views about the potential of the weighted path numbers for deriving high quality structure-property models.

Alcohols↗

PubMed2001

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. Quantitative molecular similarity analysis (QMSA) methods, based on experimental data or computed molecular descriptors, have emerged as powerful tools for analog selection and property estimation. We have carried out a comparative study of similarity spaces derived from atom pairs and a large set of topological indices for two diverse sets of chemicals: (a) a set of 469 chemicals with vapor pressure data from the TSCA inventory, and (b) a set of 213 chemicals with lipophilicity data from the STARLIST inventory. These spaces were used for the KNN-based estimation of properties (K = 1-10, 15, 20, 25). The results for the QMSA models developed in this paper are also compared with model estimates derived from hierarchical QSARs.

Models, Molecular↗

PubMed2001

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. Each similarity method is user defined. Its efficacy depends on the set of descriptors used to define the intermolecular similarity of chemicals as well as on the mathematical function used to quantify similarity. Also, similarity methods can be based on experimental data or computed molecular descriptors. We have carried out a comparative study of similarity spaces derived from experimental data vis-a-vis computed structural parameters for two sets of chemicals: (a) a diverse set of 76 chemicals derived from the TSCA Inventory and (b) the 166 structurally distinct constituents of JP-8 identified by GC/MS. Property spaces for these two sets of chemicals were created using experimental and calculated physicochemical properties. Atom pairs (APs) and topological indices calculated by POLLY v2.3 were used to create theoretical structure spaces. These spaces were used for the KNN-based estimation of properties with K=1--10, 15, 20, 25. The results will be presented with a comparative analysis of the effectiveness of property spaces and structure spaces in analog selection and property estimation.

Models, Theoretical↗

PubMed2001

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. The use of the distance indices of both kinds in structure-boiling point modeling was analyzed. Distance indices and hyper-distance indices do not lead to particularly good models for any of the three sets. When used as composite indices they give much-improved models. However, they are most useful when combined with such indices as the number of carbon atoms in a hydrocarbon, Hosoya Z index and/or total walk count index. The following standard errors of estimate are obtained for the best models based on the combination of descriptors: 2.1 degrees C (S-39), 4.4 degrees C (S-139) and 4.1 degrees C (S-178). They compare favorably with the related models in the literature.

Alkanes↗

PubMed2001

Prediction of mutagenicity utilizing a hierarchical QSAR approach.

Quantitative structure-toxicity (QSTR) models for the mutagenicity of a set of 95 aromatic amines were developed using four classes of calculated molecular descriptors, viz., topostructural, topochemical, geometrical and quantum chemical indices. Topochemical indices gave the best predictive model when the different classes of parameters were used separately. When hierarchical QSTRs were developed using all four classes of descriptors, there was a significant increase in explained variance by the addition of topochemical indices to the set of independent variables. The addition of geometrical and quantum chemical indices or log P to the set of descriptors resulted in very little improvement in model quality.

Amines↗

PubMed2000

A comparative QSAR study of benzamidines complement-inhibitory activity and benzene derivatives acute toxicity.

A novel QSAR study of benzamidines complement-inhibitory activity and benzene derivatives acute toxicity is reported and a new efficient method for selecting descriptors is used. Complement-inhibitory activity QSAR models of benzamidines contain from one to five descriptors. The best, according to fitted and cross-validated statistical parameters, is shown to be the five-descriptor model. Models with a higher number of indices did not improve over the five-descriptor model. The benzene derivatives structure-toxicity models involve up to seven linear descriptors. Multiregression models, containing up to ten nonlinear descriptors, are also reported for the sake of comparison with previously obtained additivity models. Comparison with benzamidine complement-inhibitory activity models and with benzene derivatives toxicity models from the literature favors our novel approach.

Animals↗

PubMed2000

Multiple regression analysis with optimal molecular descriptors.

We consider construction of optimal molecular descriptors to be used for multiple regression analysis of several properties of alcohols. The descriptors are obtained by considering shorter paths with variable weight x for carbon-oxygen bond in alcohol. In particular we consider as molecular descriptors paths of length 1, 2 and 3. The multiple regression analysis of the following molecular properties was examined: - log S (S = solubility), CSA (cavity surface area), log P (P = octanol/water partition), and log gamma (gamma = infinite solution activity coefficient). By minimizing the standard error of the regression for each property we found optimal variable weight.

Alcohols↗

PubMed1999

Prediction of the dermal penetration of polycyclic aromatic hydrocarbons (PAHs): a hierarchical QSAR approach.

Attempts were made to develop hierarchical quantitative structure-activity relationship (QSAR) models for the dermal penetration of polycyclic aromatic hydrocarbons (PAHs) using four classes of theoretical structural parameters; viz., topostructural, topochemical, geometric, and quantum chemical descriptors; and physicochemical properties such as molecular weight (MW) and lipophilicity (log P--octanol/water). The results show that topostructural, topochemical, and geometric descriptors and molecular weight are equally effective in predicting the dermal penetration of PAHs. Quantum chemical parameters did not make any improvements in the predictive power of the QSAR models.

Animals↗

PubMed1997

Predicting acute toxicity (LC50) of benzene derivatives using theoretical molecular descriptors: a hierarchical QSAR approach.

Four classes of theoretical structural parameters, viz., topostructural, topochemical, geometrical and quantum chemical descriptors, have been used in the development of quantitative structure-activity relationship (QSAR) models for a set of sixty-nine benzene derivatives. None of the individual classes of parameters was very effective in predicting toxicity. A hierarchical approach was followed in using a combination of the four classes of indices in QSAR model development. The results show that the hierarchical QSAR approach using the algorithmically derived molecular descriptors can estimate the LC50 values of the benzene derivatives reasonably well.

Algorithms↗

PubMed1996

Predicting blood-brain transport of drugs: a computational approach.

PURPOSE: This study was conducted to determine the efficacy of using nonempirical parameters in the estimation of blood-brain transport, inferred from central nervous system (CNS) activity, for a set of twenty-eight compounds. METHODS: A discriminant function analysis was used to construct three distinct models based on topological indices, a hydrogen-bonding parameter, and logP. RESULTS: These models correctly predict the CNS activity of twenty-seven of the twenty-eight compounds. CONCLUSIONS: Nonempirical parameters may be used effectively in the estimation the cerebrovascular penetration for known and newly designed drugs.

Blood-Brain Barrier↗