Recent Advances in QSAR Studies: Methods and Applications

ISBN-13: 9781402097829 / Angielski / Twarda / 2009 / 414 str.

Mark T. Cronin

Opis

Since the inception of this volume, the world s nancial climate has radically changed. Theemphasishasshiftedfromboomingeconomiesandeconomicgrowth totherealityofrecessionanddiminishingoutlook. Witheconomicdownturncomes opportunity, inallareasofchemistryfromresearchanddevelopmentthroughto productregistrationandriskassessment, replacementsarebeingsoughtforcostly time-consumingprocesses. Leadingamongstthereplacementsaremodelswithtrue predictivecapability. Ofthesecomputationalmodelsarepreferred. This volume addresses a broad need within various areas of the chemical industries, from pharmaceuticals and pesticides to personal products to provide computationalmethodstopredicttheeffects, activitiesandpropertiesofmolecules. Itaddressestheuseofmodelstodesignnewmoleculesandassesstheirfateand effectsbothtotheenvironmentandtohumanhealth. Thereisanemphasisrunning throughoutthisvolumetoproducerobustmodelssuitableforpurpose. Thevolume aimstoallowthereaderto nddataanddescriptorsanddevelop, discoverandutilise validmodels. Gdansk, Poland TomaszPuzyn Jackson, MS, USA JerzyLeszczynski Liverpool, UK MarkT. D. Cronin May2009 CONTENTS Part I Theory of QSAR 1 QuantitativeStructure ActivityRelationships(QSARs) ApplicationsandMethodology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Mark T. D. Cronin 1. 1. Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 1. 2. PurposeofQSAR. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 1. 3. ApplicationsofQSAR. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 1. 4. Methods. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 1. 5. TheCornerstonesofSuccessfulPredictiveModels . . . . . . . . . . . . 7 1. 6. AValidated(Q)SARoraValidPrediction? . . . . . . . . . . . . . . . . . . 9 1. 7. UsinginSilicoTechniques . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 1. 8. NewAreasforinSilicoModels. . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 1. 9. Conclusions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 2 TheUseofQuantumMechanicsDerivedDescriptorsin ComputationalToxicology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 Steven J. Enoch 2. 1. Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 2. 2. TheSchrodingerEquation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 2. 3. Hartree FockTheory. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 2. 4. Semi-EmpiricalMethods: AM1andRM1. . . . . . . . . . . . . . . . . . . . 18 2. 5. ABInitio: DensityFunctionalTheory. . . . . . . . . . . . . . . . . . . . . . . 19 2. 6. QSARforNon-ReactiveMechanismsofAcute(Aquatic) Toxicity. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19 2. 7. QSARsforReactiveToxicityMechanisms. . . . . . . . . . . . . . . . . . . 21 2. 7. 1. AquaticToxicityandSkinSensitisation. . . . . . . . . . . . . 21 2. 7. 2. QSARsforMutagenicity . . . . . . . . . . . . . . . . . . . . . . . . . 24 2. 8. FutureDirectionsandOutlook. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 2. 9. Conclusions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26 vii viii Contents 3 MolecularDescriptors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29 Viviana Consonni and Roberto Todeschini 3. 1. Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29 3. 1. 1. De nitions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29 3. 1. 2. History. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31 3. 1. 3. Theoreticalvs. ExperimentalDescriptors. . . . . . . . . . . . 33 3. 2. MolecularRepresentation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35 3. 3. TopologicalIndexes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38 3. 3. 1. MolecularGraphs. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38 3. 3. 2. De nitionandCalculationofTopologicalIndexes(TIs) 39 3. 3. 3. Graph-TheoreticalMatrixes. . . . . . . . . . . . . . . . . . . . . . . 42 3. 3. 4. ConnectivityIndexes . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48 3. 3. 5. CharacteristicPolynomial . . . . . . . . . . . . . . . . . . . . . . . . 50 3. 3. 6. SpectralIndexes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53 3. 4. AutocorrelationDescriptors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ."

Spis treści

Part I Theory of QSAR 1 Quantitative Structure-Acticity Relationships (QSAR) – Applications and Methodology Mark T. D. Cronin 2 The Use of Quantum Mechanics Derived Descriptors in Computational Toxicology Steven J. Enoch 3 Molecular Descriptors Viviana Consonni, Roberto Todeschini 4 3D-QSAR – Applications, Recent Advances and Limitations Wolfgang Sippl 5 Virtual Screening and Molecular Design Based on Hierarchical QSAR Technology Victor E. Kuz’min, A. G. Artemenko, Eugene N. Muratov, P. G. Polischuk, L. N. Ognichenko, A. V. Liahovsky, A. I. Hromov, E. V. Varlamova 6 Robust Methods in QSAR Michal Daszykowski, Ivana Stanimirova, Beata Walczak 7 Chemical Category Formation and Read Across for the Prediction of Toxicity Steven J. Enoch Part II Practical Applications 8 QSAR in Chromatography: Quantitative Structure-Retention Relationships (QSRR) Roman Kaliszan, Tomasz Baczek 9 The Use of QSAR and Computational Methods in Drug Design Fania Bajot 10 In Silico Approaches for Predicting ADME Properties Judith C. Madden 11 Prediction of Harmful Human Health Effects of Chemicals from Structure Mark T.D. Cronin 12 Chemometric Methods and Theoretical Molecular Descriptors in Predictive QSAR Modeling of the Environmental Behaviour of Organic Pollutants Paola Gramatica 13 The Role of QSAR Methodology in the Regulatory Assessment of Chemicals Andrew P. Worth 14 Nanomaterials – the Next Great Challenge for QSAR Modelers Tomasz Puzyn, Agnieszka Gajewicz, Danuta Leszczynska, Jerzy Leszczynski

O autorze

Jerzy Leszczynski, Professor of Chemistry and Presidential Distinguished Fellow, Department of Chemistry and Biochemistry, Jackson State University.

Blurb

Recent Advances in QSAR Studies: Methods and Applications presents an interdisciplinary overview on the most recent advances in QSAR studies. The first part of this volume is handbook-esque and consists of a comprehensive review of QSAR methodology written by outstanding scientists and highly experienced lecturers. It focuses on methodology and new ideas, providing readers with an idea of recent trends and developments in each part of QSAR strategy (descriptors, methods of modelling, validation). The second part of this volume highlights the interdisciplinary aspects and new areas of QSAR modelling. It outlines the theoretical framework together with practical applications. The most optimal solutions (descriptors, mathematical/statistical methods, validation) in the individual areas of interest (environmental risk assessment, drug design, etc.) are also discussed in more detail.

Recent Advances in QSAR Studies: Methods and Applications is targeted at scientists who are focussed on developing new methodologies as well as researchers who are engaged in trying to solve specific problems via QSAR. Additionally, this volume should serve as an essential reference to promote interactions between members of the academic community and industry.