Statistical Modelling of Molecular Descriptors in QSAR/QSPR

Transcription

1 Quantitative and Network Biology Statistical Modelling of Molecular Descriptors in QSAR/QSPR Bearbeitet von Matthias Dehmer, Kurt Varmuza, Danail Bonchev, Frank Emmert-Streib 1. Auflage Buch. XX, 436 S. Hardcover ISBN Format (B x L): 17 x 24 cm Gewicht: 1017 g Weitere Fachgebiete > Chemie, Biowissenschaften, Agrarwissenschaften > Entwicklungsbiologie > Bioinformatik Zu Leseprobe schnell und portofrei erhältlich bei Die Online-Fachbuchhandlung beck-shop.de ist spezialisiert auf Fachbücher, insbesondere Recht, Steuern und Wirtschaft. Im Sortiment finden Sie alle Medien (Bücher, Zeitschriften, CDs, ebooks, etc.) aller Verlage. Ergänzt wird das Programm durch Services wie Neuerscheinungsdienst oder Zusammenstellungen von Büchern zu Sonderpreisen. Der Shop führt mehr als 8 Millionen Produkte.

2 V Preface XIII List of Contributors XV 1 Current Modeling Methods Used in QSAR/QSPR 1 Liew Chin Yee and Yap Chun Wei 1.1 Introduction Modeling Methods Methods for Regression Problems Multiple Linear Regression Partial Least Squares Feedforward Backpropagation Neural Network General Regression Neural Network Gaussian Processes Methods for Classification Problems Logistic Regression Linear Discriminant Analysis Decision Tree and Random Forest k-nearest Neighbor Probabilistic Neural Network Support Vector Machine Software for QSAR Development Structure Drawing or File Conversion D Structure Generation Descriptor Calculation Modeling General purpose Conclusion 24 References 26

3 VI 2 Developing Best Practices for Descriptor-Based Property Prediction: Appropriate Matching of Datasets, Descriptors, Methods, and Expectations 33 Michael Krein, Tao-Wei Huang, Lisa Morkowchuk, Dimitris K. Agrafiotis, and Curt M. Breneman 2.1 Introduction Posing the Question Validating the Models Interpreting the Models Leveraging Experimental Data and Understanding their Limitations Descriptors: The Lexicon of QSARs Classical QSAR Descriptors and Uses Experimentally Derived Descriptors Biodescriptors Descriptors from Spectroscopy/Spectrometry and Microscopy D, 1D and 2D Computational Descriptors D Descriptors and Beyond Local Molecular Surface Property Descriptors Quantum Chemical Descriptors Machine Learning Methods: The Grammar of QSARs Principal Component Analysis Factor Analysis Multidimensional Scaling, Stochastic Proximity Embedding, and Other Nonlinear Dimensionality Reduction Methods Clustering Partial Least Squares (PLS) k-nearest Neighbors (knn) Neural Networks Ensemble Models Decision Trees and Random Forests Kernel Methods Ranking Methods Defining Modeling Strategies: Putting It All Together Conclusions 56 References 57 3 Mold 2 Molecular Descriptors for QSAR 65 Huixiao Hong, Svetoslav Slavov, Weigong Ge, Feng Qian, Zhenqiang Su, Hong Fang, Yiyu Cheng, Roger Perkins, Leming Shi, and Weida Tong 3.1 Background History of QSAR Introduction to QSAR Molecular Descriptors: Bridge for QSAR Molecular Descriptors Role of Molecular Descriptors 70

4 VII Types of Molecular Descriptors Calculation of Molecular Descriptors (Software Packages) Mold 2 Molecular Descriptors Description of Mold 2 Descriptors Topological Descriptors Constitutional Descriptors Information Content-based Descriptors Calculation of Mold 2 Descriptors Evaluation of Mold 2 Descriptors Information Content by Shannon Entropy Analysis Correlations between Descriptors QSAR Using Mold 2 Descriptors Classification Models based on Mold 2 Descriptors Regression Models based on Mold 2 Descriptors Conclusion Remarks 105 References Multivariate Analysis of Molecular Descriptors 111 Viviana Consonni and Roberto Todeschini 4.1 Introduction D Matrix-Based Descriptors Graph-Theoretical Matrices Vertex Weighting Schemes Multivariate Similarity Analysis of Chemical Spaces Analysis of Chemical Information of Descriptors from Graph-Theoretical Matrices Data Sets Comparison of Graph-Theoretical Matrices Comparison of Weighted Graph-Theoretical Matrices Comparison of Matrix Operators Comparison of Single Operators from Different Graph-Theoretical Matrices Conclusions 143 References Partial-Order Ranking and Linear Modeling: Their Use in Predictive QSAR/QSPR Studies 149 Andrew G. Mercader and Eduardo A. Castro 5.1 Introduction Linear QSAR Methodology, ERM, RM and GA Replacement Method Enhanced Replacement Method Genetic Algorithm Main Differences between MRM and RM Principles of Ranking Methods 159

5 VIII 5.4 Selection of the Molecular Descriptors for Ranking QSAR Based on Hasse Diagrams Discussion Conclusions 169 References Graph-Theoretical Descriptors for Branched Polymers 175 Koh-Hei Nitta 6.1 Introduction Algebraic Graph Theory Ideal Chain Models Graph-Theoretical Approach to Chain Dynamics and Statistics Radius of Gyration Rouse Dynamics Intrinsic Viscosity Scattering Function High Moments of Relaxation Time and Radius of Gyration Applications Final Remarks 194 References Structural-Similarity-Based Approaches for the Development of Clustering and QSPR/QSAR Models in Chemical Databases 201 Irene Luque Ruiz, Gonzalo Cerruela García, and Miguel Ángel Gómez-Nieto 7.1 Chemical Structural Similarity Molecular Graph and Structural Similarity Descriptor-Based Structural Similarity Combining Structural Similarity Approaches Approximate Structural Similarity Clustering Models Based on Structural Similarity Clustering of Chemical Databases Pattern Representation of Chemicals Structures Clustering of Chemical Databases QSPR/QSAR Models Based on Structural Similarity Dataset Selection Dataset Representation Fitting of the Dataset Representation Building and Validation of the QSAR Model 221 References Statistical Methods for Predicting Compound Recovery Rates for Ligand- Based Virtual Screening and Assessing the Probability of Activity 229 Martin Vogt and Jürgen Bajorath 8.1 Introduction Theory 231

6 IX Bayesian Approach to Virtual Screening Predicting the Performance of Bayesian Screening Practical Prediction of Compound Recall Exemplary Results Alternative Approaches to the Prediction of Compound Recall Conclusions 240 References Molecular Descriptors and the Electronic Structure 245 Bögel Horst 9.1 Introduction The Structure of Molecules General Remarks Structure Coding Structural Features Structure and Energy The Electronic Structure Dividing Molecules in Atoms and Bonds Bonding in Molecules Energy Partitioning Energy and the Hückel Approach Energy Components of Atoms and Bonds Perturbation Treatment of the Electronic Structure Thermodynamic Equilibrium Model of Atom in Molecules Structure and Dynamics Molecular Flexibility Molecular Dynamics Simulation Conformational Space Structure and Properties Structure Property Relationships Type of Molecular Properties Molecular Commonality and Similarity Multilinear Regression Selection of Molecular Descriptors Modeling of Physicochemical Properties of the Isomers of Hexane Modeling of the Proton Affinity Proton Affinity of Pyridines Data and Mechanism Model I Model II Model III Model IV Model V Model VI 282

7 X Basicity of N-Heterocyclic Aromatics Molecular Surface Properties Conclusions 290 References New Types of Descriptors and Models in QSAR/QSPR 293 Christian Kramer and Timothy Clark 10.1 Introduction Local Properties Molecular Electrostatic Potential Electron Density Local Polarizability Local Ionization Energy and Local Electron Affinity Descriptors Derived from Local Properties PEST Methodology MEP as Descriptor for Hydrogen-Bonding Strengths ParaSurf (Politzer Murray) Descriptors D: Conformational-Ensemble-based Descriptors Proper Validation/Generation of QSA(P)R Models Conclusions 302 References Consensus Models of Activity Landscapes 307 José L. Medina-Franco, Austin B. Yongye, and Fabian López-Vallejo 11.1 Introduction Characterization of the Activity Landscape Consensus Models of Activity Landscape Chemical Space and Molecular Representation Activity Landscape with Multiple Representations Conclusions and Future Perspectives 322 References Reverse Engineering Chemical Reaction Networks from Time Series Data 327 Dominic P. Searson, Mark J. Willis, and Allen Wright 12.1 Introduction Problem Definition Reconstruction of Elementary Reaction Networks from Data by Network Search Network Search as a Nonlinear Integer Programming Problem Estimation of the Rate Coefficients for Trial Reaction Networks Formulation of the Objective Function for Network Search Physical/Chemical Information Available No physical/chemical Information Available 336

8 XI 12.5 Differential Evolution for Searching the Space of Reaction Networks Basic DE Optimization Method Self-Adaptive DE with Integer Variables Network Identification Case Studies Estimation of Time Derivatives DE Settings Model Selection Methodology Results Conclusions 346 References Reduction of Dimensionality, Order, and Classification in Spaces of Theoretical Descriptions of Molecules: An Approach Based on Metrics, Pattern Recognition Techniques, and Graph Theoretic Considerations 349 George Maroulis 13.1 Introduction Theory Methods and Computational Strategy Results and Discussion Conclusions 363 References The Analysis of Organic Reaction Pathways by Brownian Processing 365 Daniel J. Graham 14.1 Introduction Electronic Messages, Information, and Energy Molecular Messages, Conversions, and State Space Representations Closing 389 References Generation of Chemical Transformations: Reaction Pathways Prediction and Synthesis Design 393 Graz_ yna Nowak and Grzegorz Fic 15.1 Introduction The Graph Transformation Rules for Generation of Chemical Reactions The Graph-Theoretic Reaction Rules and Formal-Logical Approach for Reaction Generation The Chemical Reaction Graph Ugi and Dugundji Formal Theory for Reactions and Reaction Mechanisms 400

9 XII The Empirical Reaction Rules and Knowledge-Based Approach for Reaction Generation. Automated Creation of Rules by Learning and Reaction Database Mining Automatically Derived Reaction Rules Functional Group Transformations Substructure-Based Transformations Combinatorial Complexity Problem: Strategies for the Directed Reaction Generation Retrosynthetic Generation of Chemical Transformations: Computer-Assisted Synthesis Design Recognition of Guiding Patterns, Molecular Symmetry, or Isomorphic Substructures Complexity-Based Disconnective Strategies Concept of the Strategic Bond Tree for Disconnections Forward Generation of Chemical Transformations: Computer-Assisted Reaction Prediction Quantitative Models for Reactivity Prediction Formal-Logical Approach to the Search Space of Possible Chemical Transformations Conclusion 419 References 420 Index 427