Accurate and interpretable computational modeling of chemical mutagenicity

We describe a method for modeling chemical mutagenicity in terms of simple rules based on molecular features. A classification model was built using a rule-based ensemble method called RuleFit, developed by Friedman and Popescu. We show how performance compares favorably against literature methods. Performance was measured through the use of cross-validation and testing on external test sets. All data sets used are publicly available. The method automatically generated transparent rules in terms of molecular structure that agree well with known toxicology. While we have focused on chemical mutagenicity in demonstrating this method, we anticipate that it may be more generally useful in modeling other molecular properties such as other types of chemical toxicity.     

Operator space tensor products of <Emphasis Type="Italic">C</Emphasis>*-algebras

For C*-algebras A and B, the identity map from into A _λ B is shown to be injective. Next, we deduce that the center of the completion of the tensor product A⊗B of two C*-algebras A and B with centers Z(A) and Z(B) under operator space projective norm is equal to . A characterization of isometric automorphisms of and A _h B is also obtained. Dedicated to Ajit Iqbal Singh on her 65th birthday.     

Prediction of anti-HIV activity and cytotoxicity of pyrimidinyl and triazinyl amines: A QSAR study

A QSAR study on a series of pyrimidinyl and triazinyl amines was performed to explore the physico-chemical parameters responsible for their anti-HIV activity and cytotoxicity. Physico-chemical parameters were calculated using WIN CAChe 6.1. Stepwise multiple linear regression analysis was carried out to derive QSAR models which were further evaluated for statistical significance and predictive power by internal and external validation. The selected best QSAR models showed correlation coefficient R of 0.914 and 0.901, and cross-validated squared correlation coefficient Q ² of 0.685 and 0.691 for anti-HIV activity and cytotoxicity, respectively. The developed significant QSAR model indicates that hydrophobicity of the whole molecule plays an important role in the anti-HIV activity and cytotoxicity of pyrimidinyl and triazinyl amine derivatives. When hydrophobicity is increased, anti-HIV activity of the present series of compounds is decreased leading to high cytotoxicity.     

1H and 13C assignments of five cembrenes from guggul

Chemical shift assignments of (1)H and (13)C of five cembrene compounds isolated from the hexane extract of guggul, the resin of Commiphora mukul, are reported. Using (1)H, (13)C, and 2D NMR methods their structures were determined as cembrene (1-isopropyl-4,8,12-trimethyl-cyclotetradeca-2,4,7,11-tetraene), cembrene A (1-isopropenyl-4,8,12-trimethyl-cyclotetradeca-4,8,12-triene), cembrenol (1-isopropyl-4,8,12-trimethyl-cyclotetradeca-3,7,11-trienol), mukulol (1-isopropyl-4,8,12-trimethyl- cyclotetradeca-3,7,11-trienol), and verticillol (4,8,12,15,15-pentamethyl-bicyclo[9.3.1]pentadeca-3,7-dien-12-ol).     

Customizing scoring functions for docking

Empirical scoring functions used in protein-ligand docking calculations are typically trained on a dataset of complexes with known affinities with the aim of generalizing across different docking applications. We report a novel method of scoring-function optimization that supports the use of additional information to constrain scoring function parameters, which can be used to focus a scoring function’s training towards a particular application, such as screening enrichment. The approach combines multiple instance learning, positive data in the form of ligands of protein binding sites of known and unknown affinity and binding geometry, and negative (decoy) data of ligands thought not to bind particular protein binding sites or known not to bind in particular geometries. Performance of the method for the Surflex-Dock scoring function is shown in cross-validation studies and in eight blind test cases. Tuned functions optimized with a sufficient amount of data exhibited either improved or undiminished screening performance relative to the original function across all eight complexes. Analysis of the changes to the scoring function suggest that modifications can be learned that are related to protein-specific features such as active-site mobility.     

A facial microwave-assisted synthesis, spectroscopic characterization and preliminary complexation studies of calix[4]pyrroles containing the hydroxamic-acid moiety

The synthesis, spectroscopic characterization and preliminary complexation properties of functionalized calix[4]pyrroles are described. To date, two generalized preparative approaches have been pursued (i) modifying the basic pyrrole-plus-ketone synthesis of calix[4]pyrrole by using microwave irradiation protocol, (ii) the basic meso-tetra(methyl) meso-tetra(p-nitrophenyl) calix[4]pyrrole skeleton was functionalized to give hydroxamic acids, especially in the meso-position of the macrocycles. The structures of novel calix[4]pyrrole hydroxamic acid derivatives were confirmed on the basis of various physico-chemical techniques such as elemental analysis, FT-IR, ¹H NMR and FAB-Mass. The results of preliminary studies on the extraction of vanadium (V) with the host calix[4]pyrrole hydroxamic acids were elucidated by significant examination of UV–Vis spectroscopy and ICP-AES. Single crystal structure of basic meso-tetra(methyl) meso-tetra (p-nitro phenyl) calix[4]pyrrole moiety has also been reported.     

Coagulation of nanoparticles in reverse micellar systems: a Monte Carlo model

The process of formation of nanoparticles obtained by mixing two micellized, aqueous solutions has been simulated using the Monte Carlo technique. The model includes the phenomena of finite nucleation, growth via intermicellar exchange, and coagulation of nanoparticles after their formation. Using the model, an exploratory study has been conducted to analyze whether the coagulation of nanoparticles is the reason for the formation of nanoparticles whose sizes are comparable to the size of the reverse micelles. The model explains the possible mechanism of coagulation of semiconductor nanoparticles formed within reverse micelles and its effect on the evolution of their size with time. The model is predictive in nature, and the simulation results compare well with those observed experimentally.     

Enforcing solution phase nanoscopic aggregation in a palindromic tripeptide

C-terminal dimerization of a tripeptide palindrome afforded fibrillation in solution through an assembly probably driven by hydrogen bonding and hydrophobic contributions; such an approach provides an expeditious entry into fabrication of fibrillating peptides from non-fibrillating peptide sequences.     

Relationship between torsional frequency and potential barrier height forAB n type molecular system

A relationship between the torsional frequency (v ₁₀) and the potential barrier (V _n) has been determined forAB _n type molecular system havingn-fold symmetry axis. It is found thatv ₁₀ varies prominently asV _n ^1/2 ,V _n andV _n ² in certain ranges. TheV _n value computed fromv ₁₀ andI* _r has been compared with that obtained from other experimental data for someAB _n units in different molecular-crystalline systems. Although there is in general a good agreement, in some cases the values differ significantly, perhaps due to the erroneous assignment of torsional mode and/or the large errors in theV _n value obtained from other experimental data.