Usporedba QSPR modela zasnovanih na vodikom-popunjenim molekularnim grafovima i na grafovima atomskih orbitala

QSPR models are studied for normal boiling points of alkanes, alkylbenzenes, and polyaromatic hydrocarbons, in terms of optimized correlation weights of local invariants of the hydrogen- -filled graphs (HFGs) and of the graphs of atomic orbitals (GAOs). Morgan extended connectivities of the zeroth, first, and second order of the HFGs and GAOs were employed. The best QSPR model obtained is based on optimized correlation weights of the extended connectivity of the first order of the GAO. The statistical characteristics of this model are: n = 70, r superscript(2) = 0.9988, s = 5.8 °C, F = 57437 (training set); n = 70, r superscript(2) = 0.9985, s = 6.7 °C, F = 45154 (test set).Istraživani su QSPR modeli za normalnu točku vrelišta alkana, alkilbenzena i poliaromatskih ugljikovodika, zasnovani na optimiziranim korelacijskim te`inama lokalnih invarijanti vodikom-popunjenih molekularnih grafova (HFG) i grafova atomskih orbitala (GAO). Primjenjeni su Morganovi indeksi proširene povezanosti nultoga, prvoga i drugoga reda, kako za HFG tako i za GAO. Najbolji QSPR model je dobiven na osnovi optimiziranih korelacijskih težina za proširenu povezanost prvoga reda za GAO. Statističke karakteristike ovoga modela su: n = 70, r superscript(2) = 0.9988, s = 5.8 °C, F = 57437 (training set); n = 70, r superscript(2) = 0.9985, s = 6.7 °C, F = 45154 (test set)

Advancement of predictive modeling of zeta potentials (ζ) in metal oxide nanoparticles with correlation intensity index (CII)

It was expected that index of the ideality of correlation (IIC) and correlation intensity index (CII) could be used as possible tools to improve the predictive power of the quantitative model for zeta potential of nanoparticles. In this paper, we test how the statistical quality of quantitative structure-activity models for zeta potentials (ζ, a common measurement that reflects surface charge and stability of nanomaterial) could be improved with the use of these two indexes. Our hypothesis was tested using the benchmark data set that consists of 87 measurements of zeta potentials in water. We used quasi-SMILES molecular representation to take into consideration the size of nanoparticles in water and calculated optimal descriptors and predictive models based on the Monte Carlo method. We observed that the models developed with utilization of CII are statistically more reliable than models obtained with the IIC. However, the described approach gives an improvement of the statistical quality of these models for the external validation sets to the detriment for the training sets. Nevertheless, this circumstance is rather an advantage than a disadvantage

QSAR Model for Cytotoxicity of Silica Nanoparticles on Human Embryonic Kidney Cells1

Abstract A predictive model for cytotoxicity of 20 and 50 nm silica nanoparticles has been built using so-called optimal descriptors as mathematical functions of size, concentration and exposure time. These parameters have been encoded into 31 combinations 'concentration-exposure-size'. The calculation has been carried out by means of the CORAL software ( http://www.insilico.eu/coral/ ) using three random splits of the obtained systems into training and test sets. The statistical quality of the best model for cell viability (%) of cultured human embryonic kidney cells (HEK293) exposed to different concentrations of silica nanoparticles measured by MTT assay is satisfactory

QSPR modelling of normal boiling points and octanol/water partition coefficient for acyclic and cyclic hydrocarbons using SMILES-based optimal descriptors

AbstractPredictive quantitative structure - property relationships (QSPR) have been established for normal boiling points and octanol/water partition coefficient for acyclic and cyclic hydrocarbons using optimal descriptors calculated with simplified molecular input line entry system (SMILES). The probabilistic criteria for a rational definition of the domain of applicability of these models are discussed

CORAL: the prediction of biodegradation of organic compounds with optimal SMILES-based descriptors

Abstract CORAL software (http:/www.insilico.eu/coral) has been used to build up quantitative structure-biodegradation relationships (QSPR). The normalized degradation percentage has been used as the measure of biodegradation (for diverse organic compounds, n=445). Six random splits into sub-training, calibration, and test sets were examined. For each split the QSPR one-variable linear regression model based on the SMILES-based optimal descriptors has been built up. The average values of numbers of compounds and the correlation coefficients (r2) between experimental and calculated biodegradability values of these six models for the test sets are n=88.2±11.7 and r2=0.728±0.05. These six models were further tested against a set of chemicals (n=285) for which only categorical values (biodegradable or not) were available. Thus we also evaluated the use of the model as a classifier. The average values of the sensitivity, specificity, and accuracy were 0.811±0.019, 0.795±0.024, and 0.803±0.008, respectively

Nano-QSAR: Model of mutagenicity of fullerene as a mathematical function of different conditions

The experimental data on the bacterial reverse mutation test (under various conditions) on C60 nanoparticles for the cases (i) TA100, and (ii) WP2uvrA/pkM101 are examined as endpoints. By means of the optimal descriptors calculated with the Monte Carlo method a mathematical model of these endpoints has been built up. The models are a mathematical function of eclectic data such as (i) dose (g/plate); (ii) metabolic activation (i.e. with mix S9 or without mix S9); and (iii) illumination (i.e. darkness or irradiation). The eclectic data on different conditions were represented by so-called quasi-SMILES. In contrast to the traditional SMILES which are representation of molecular structure, the quasi-SMILES are representation of conditions by sequence of symbols. The calculations were carried out with the CORAL software, available on the Internet at http://www.insilico.eu/coral. The main idea of the suggested descriptors is the accumulation of all available eclectic information in the role of logical and digital basis for building up a model. The computational experiments have shown that the described approach can be a tool to build up models of mutagenicity of fullerene under different conditions

QSPR modeling of Gibbs free energy of organic compounds by weighting of nearest neighboring codes

We examine the encoding of chemical structure of organic compounds by Labeled Hydrogen-Filled Graphs (LHFGs). Quantitative Structure-Property Relationships (QSPR) for a representative set of 150 organic molecules have been derived by means of the optimization of correlation weights of local invariants of the LHFGs. We have tested as local invariants Morgan extended connectivity of zero- and first order, numbers of path of length 2 (P2) and valence shells of distance of 2 (S2) associated with each atom in the molecular structure, and the Nearest Neighboring Codes (NNC). The best statistical characteristics for the Gibbs free energy has been obtained for the NNC weighting. Statistical parameters corresponding to this model are the following n = 100, r2 = 0.9974, s = 5.136 kJ/mol, F = 38319 (training set); n = 50, r2 = 0.9990, s = 3.405 kJ/mol, F = 48717 (test set). Some possible further developments are pointed out.Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicada

CORAL Models for Drug-Induced Nephrotoxicity

Drug-induced nephrotoxicity is a major cause of kidney dysfunction with potentially fatal consequences. The poor prediction of clinical responses based on preclinical research hampers the development of new pharmaceuticals. This emphasises the need for new methods for earlier and more accurate diagnosis to avoid drug-induced kidney injuries. Computational predictions of drug-induced nephrotoxicity are an attractive approach to facilitate such an assessment and such models could serve as robust and reliable replacements for animal testing. To provide the chemical information for computational prediction, we used the convenient and common SMILES format. We examined several versions of so-called optimal SMILES-based descriptors. We obtained the highest statistical values, considering the specificity, sensitivity and accuracy of the prediction, by applying recently suggested atoms pairs proportions vectors and the index of ideality of correlation, which is a special statistical measure of the predictive potential. Implementation of this tool in the drug development process might lead to safer drugs in the future

EFSA's OpenFoodTox: An open source toxicological database on chemicals in food and feed and its future developments

Since its creation in 2002, the European Food Safety Authority (EFSA) has produced risk assessments for over 5000 substances in >2000 Scientific Opinions, Statements and Conclusions through the work of its Scientific Panels, Units and Scientific Committee. OpenFoodTox is an open source toxicological database, available both for download and data visualisation which provides data for all substances evaluated by EFSA including substance characterisation, links to EFSA's outputs, applicable legislations regulations, and a summary of hazard identification and hazard characterisation data for human health, animal health and ecological assessments. The database has been structured using OECD harmonised templates for reporting chemical test summaries (OHTs) to facilitate data sharing with stakeholders with an interest in chemical risk assessment, such as sister agencies, international scientific advisory bodies, and others. This manuscript provides a description of OpenFoodTox including data model, content and tools to download and search the database. Examples of applications of OpenFoodTox in chemical risk assessment are discussed including new quantitative structure–activity relationship (QSAR) models, integration into tools (OECD QSAR Toolbox and AMBIT-2.0), assessment of environmental footprints and testing of threshold of toxicological concern (TTC) values for food related compounds. Finally, future developments for OpenFoodTox 2.0 include the integration of new properties, such as physico-chemical properties, exposure data, toxicokinetic information; and the future integration within in silico modelling platforms such as QSAR models and physiologically-based kinetic models. Such structured in vivo, in vitro and in silico hazard data provide different lines of evidence which can be assembled, weighed and integrated using harmonised Weight of Evidence approaches to support the use of New Approach Methodologies (NAMs) in chemical risk assessment and the reduction of animal testing