| 1. |
- Bergström, Christel A S, et al.
(författare)
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Global and local computational models for aqueous solubility prediction of drug-like molecules.
- 2004
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Ingår i: Journal of chemical information and computer sciences. - : American Chemical Society (ACS). - 0095-2338 .- 1520-5142. ; 44:4, s. 1477-88
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to develop in silico protocols for the prediction of aqueous drug solubility. For this purpose, high quality solubility data of 85 drug-like compounds covering the total drug-like space as identified with the ChemGPS methodology were used. Two-dimensional molecular descriptors describing electron distribution, lipophilicity, flexibility, and size were calculated by Molconn-Z and Selma. Global minimum energy conformers were obtained by Monte Carlo simulations in MacroModel and three-dimensional descriptors of molecular surface area properties were calculated by Marea. PLS models were obtained by use of training and test sets. Both a global drug solubility model (R(2) = 0.80, RMSE(te) = 0.83) and subset specific models (after dividing the 85 compounds into acids, bases, ampholytes, and nonproteolytes) were generated. Furthermore, the final models were successful in predicting the solubility values of external test sets taken from the literature. The results showed that homologous series and subsets can be predicted with high accuracy from easily comprehensible models, whereas consensus modeling might be needed to predict the aqueous drug solubility of datasets with large structural diversity.
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| 2. |
- Blurock, Edward
(författare)
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Detailed mechanism generation. 1. Generalized reactive properties as reaction class substructures
- 2004
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Ingår i: Journal of Chemical Information and Computer Sciences. - : American Chemical Society (ACS). - 0095-2338 .- 1520-5142. ; 44:4, s. 1336-1347
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Tidskriftsartikel (refereegranskat)abstract
- This paper, the first in a series on the automatic generation of detailed hydrocarbon mechanisms for hydrocarbons, describes how generalized reaction types, specifically the 25 types outlined by Curran et al. for heptane and isooctane combustion, can be translated into general reaction classes. Each type description from Curran et al. ranges from specific, such as differentiating among 1degrees, 2degrees, and 3degrees centers, to nonspecific such as specifying intermediate specific as "products". In the latter case, additional interpretation of the reaction type must be extrapolated from other sources. The types are translated to the substructure "patterns" representing reaction classes. The success of fully translating all the rate and structural information described in these reaction types as they are defined in the literature demonstrates the power of the approach used here. A comparison of the generated reactions using these 25 types with that of a hand-produced heptane mechanism showed that, aside from well-defined exceptions, the set of reactions were almost identical. Often just the elimination of selected species (and sometimes reactions) was enough to make them identical. A notable exception was the use of lumped species in the hand-produced mechanism. The purpose of this paper is to show that an established set of reaction type descriptions can be translated to reaction classes suitable for automatic mechanism generation. A further goal of this paper is to show that these classes can be used to generate a detailed mechanism that mimics a hand produced one.
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| 3. |
- Blurock, Edward
(författare)
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Detailed mechanism generation. 2. Aldehydes, ketones, and olefins
- 2004
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Ingår i: Journal of Chemical Information and Computer Sciences. - : American Chemical Society (ACS). - 0095-2338 .- 1520-5142. ; 44:4, s. 1348-1357
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Tidskriftsartikel (refereegranskat)abstract
- Generalized reaction classes for the consumption and decomposition of aldehydes, ketones, and olefins are described. These classes are important for generating not only reactions for the consumption of the branching agents of low-temperature hydrocarbon combustion but also reactions of the oxidation of alkenes and the decomposition of cyclic ethers. These reaction classes have been extrapolated from specific reactions of existing validated mechanisms. The reaction patterns making up the class were derived by identifying the reactive center of the specific reactions and the important surrounding functional groups. The rates used currently are definitely "first guesses" based on these specific reactions. The reaction classes in this paper supplement the reaction classes derived from accepted reaction types in the previous paper in this series. The purpose of this paper is to outline a complete (with very few exceptions) set of reaction classes which describe the C-5 and C-6 products of the low-temperature and cyclic ether path in the heptane and isooctane mechanisms.
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| 4. |
- Cherkasov, A., et al.
(författare)
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A new method for estimation of homolytic C-H bond dissociation enthalpies
- 2000
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Ingår i: Journal of chemical information and computer sciences. - : American Chemical Society (ACS). - 0095-2338 .- 1520-5142. ; 40:5, s. 1222-1226
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Tidskriftsartikel (refereegranskat)abstract
- In this work we have quantitatively analyzed substituent effects on the homolytic bond dissociation enthalpy of 79 different compounds using a method based on discrete distance dependent atomic contributions to a molecular property. The resulting empirical relationship can be used to predict C-H bond dissociation enthalpies (within +/-10 kJ mol(-1)) for molecules where resonance contributions and captodative stabilization are insignificant. For species where captodative stabilization of the corresponding C-centered radical is possible, the method clearly overestimates the C-H bond dissociation enthalpy.
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| 5. |
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| 6. |
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| 7. |
- Engkvist, Ola, et al.
(författare)
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On the relation between retention indexes and the interaction between the solute and the column in gas-liquid chromatography
- 1996
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Ingår i: Journal of chemical information and computer sciences. - : American Chemical Society (ACS). - 0095-2338 .- 1520-5142. ; 36:6, s. 1153-1161
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Tidskriftsartikel (refereegranskat)abstract
- Gas-liquid chromatography retention indexes for organic molecules are determined by the interaction between the molecule and the column liquid phase. In this article, a model for calculating the interaction energy between a molecule and a dielectric wall is developed. The model is at least to our knowledge the first attempt to predict retention indexes from the interaction between the molecules and the column. This approach to predict retention indexes is radically different from methods proposed before. Earlier predictions of the retention indexes have been done by a large number of descriptors, which were Linearly correlated to the retention indexes. The developed model has been tested for polycyclic aromatic hydrocarbons mainly with a molecular weight of 302. For the molecules with MW 302 the obtained correlation coefficient is 0.92. A somewhat simpler model is used to fit PAH with different MWs. A correlation coefficient of 0.998 is obtained if the retention indexes were fitted to the logarithm of the interaction energies between the PAHs and the column.
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| 8. |
- Koppisetty, Ashok Krishna Chaitanya, 1982, et al.
(författare)
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Computation of Binding Energies Including Their Enthalpy and Entropy Components for Protein-Ligand Complexes Using Support Vector Machines
- 2013
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Ingår i: Journal of Chemical Information and Modeling. - : American Chemical Society (ACS). - 1549-9596 .- 1549-960X .- 0095-2338 .- 1520-5142. ; 53:10, s. 2559-2570
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Tidskriftsartikel (refereegranskat)abstract
- Computing binding energies of protein-ligand complexes including their enthalpy and entropy terms by means of computational methods is an appealing approach for selecting initial hits and for further optimization in early stages of drug discovery. Despite the importance, computational predictions of thermodynamic components have evaded attention and reasonable solutions. In this study, support vector machines are used for developing scoring functions to compute binding energies and their enthalpy and entropy components of protein-ligand complexes. The binding energies computed from our newly derived scoring functions have better Pearson's correlation coefficients with experimental data than previously reported scoring functions in benchmarks for protein-ligand complexes from the PDBBind database. The protein-ligand complexes with binding energies dominated by enthalpy or entropy term could be qualitatively classified by the newly derived scoring functions with high accuracy. Furthermore, it is found that the inclusion of comprehensive descriptors based on ligand properties in the scoring functions improved the accuracy of classification as well as the prediction of binding energies including their thermodynamic components. The prediction of binding energies including the enthalpy and entropy components using the support vector machine based scoring functions should be of value in the drug discovery process.
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| 9. |
- Öberg, Tomas, 1956-
(författare)
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Boiling points of halogenated aliphatic compounds : a quantitative structure-property relationship for prediction and validation.
- 2004
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Ingår i: Journal of chemical information and computer sciences. - : American Chemical Society. - 0095-2338 .- 1520-5142. ; 44:1, s. 187-192
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Tidskriftsartikel (refereegranskat)abstract
- Halogenated aliphatic compounds have many technical uses, but substances within this group are also ubiquitous environmental pollutants that can affect the ozone layer and contribute to global warming. The establishment of quantitative structure-property relationships is of interest not only to fill in gaps in the available database but also to validate experimental data already acquired. The three-dimensional structures of 240 compounds were modeled with molecular mechanics prior to the generation of empirical descriptors. Two bilinear projection methods, principal component analysis (PCA) and partial-least-squares regression (PLSR), were used to identify outliers. PLSR was subsequently used to build a multivariate calibration model by extracting the latent variables that describe most of the covariation between the molecular structure and the boiling point. Boiling points were also estimated with an extension of the group contribution method of Stein and Brown.
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| 10. |
- Andersson, Patrik, et al.
(författare)
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General and Class Specific Models for Prediction of Soil Sorption Using Various Physicochemical Descriptors
- 2002
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Ingår i: Journal of Chemical Information and Modeling. - : American Chemical Society (ACS). - 0095-2338. ; 42:6, s. 1450-9
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Tidskriftsartikel (refereegranskat)abstract
- Diverse chemical descriptors were explored for use in QSAR models aimed to screen the soil sorption potential of organic compounds. The descriptors included logP, HyperChem QSARProperties descriptors, a combination of connectivity indices, geometrical, and quantum chemical measures, and two sets from the DRAGON and CODESSA program packages, respectively. Generally, the univariate logP models were capable of capturing most of the variation and give an indication of the sorption potential. The multivariate models required refined variable selection procedures but were shown to include crucial descriptors for modeling compound classes with specific chemical characteristics.
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