Contents 1 Open-Source Tools, Techniques, and Data in Chemoinformatics

Transcription

1 Contents 1 Open-Source Tools, Techniques, and Data in Chemoinformatics Chemoinformatics Open-Source Tools Introduction to Programming Languages Chemical Structure Representation Code for Including the Editor Applet in JChemPaint Definition of Templates (Polygons, Benzene, Bond, Atom, etc.) Free Tools Academic Programs Marvin Sketch ACD Labs Commercial Tools ChemDraw Schrodinger MOE (CCG) Accelrys A Practice Tutorial Interconversion of Name/SMILES to Structure and Vice Versa Introduction to Chemical Structure Formats Linear Format Graph-based Representation (2D and 3D formats) Connection Tables FILE FORMATS D and 3D Representation Code for 3D Structure Generation in ChemAxon A Practice Tutorial Abstract Representation of Molecules File Format Exchange A Practice Tutorial Code for Reading a Molecule, checking the Number of Atoms, and Writing a SMILES String xiii

2 xiv Contents Code for Reading a SMILES String in Python Similarity and Fingerprint Analysis Simple Fingerprints (Structural Keys) Hashed Fingerprints A Practice Tutorial Molecular Similarity Exact Structure Search Substructure Search Similarity Search Subsimilarity Search Search for Relationship Similarity Measures Molecular Diversity Advanced Structure-handling Tools CCML ChemXtreme Barcoding SMILES Chem Robot Image to Structure Tools CLide Advanced Structure Computation Platforms Virtual Library Enumeration Clustering Databases Database Server My SQL Code for Connecting to a MySQL Database A Practice Tutorial Creating and Hosting Database A Practice Tutorial Hosting the Database Chemical Databases Do It Yourself (DIY) Questions References Chemoinformatics Approach for the Design and Screening of Focused Virtual Libraries Introduction to Structure Property Correlations Descriptors Online Property Prediction Tools Virtual Library Generation (Enumeration) Virtual Screening Thumb Rules for Computing Molecular Properties Do it Yourself Questions References

3 Contents xv 3 Machine Learning Methods in Chemoinformatics for Drug Discovery Introduction Machine Learning Models for Predictive Studies Machine Learning Methods Open-Source Tools for Building Models for Drug Design Library for Support Vector Machines (LibSVM) Waikato Environment for Knowledge Analysis (WeKa) R Program Free Tools for Machine Learning An Example of SVR-based Machine Learning Rapid Miner Commercial Tools for Building ML Models Molecular Operating Environment (MOE) IBM SPSS Matrix Laboratory (MATLAB) Genetic Programming-Based ML Models A Practical Demonstration of GP-Based Software Thumb Rules for Machine Learning-Based Modelling Do it Yourself (DIY) Questions References Docking and Pharmacophore Modelling for Virtual Screening Introduction A Practice Tutorial: Docking Using a Commercial Tool Docking Using Open Source Software Autodock Steps Docking Using AutoDock Vina Other Docking Algorithms Induced Fit Docking Flexible Protein Docking Blind Docking Cross Docking Docking and Site-Directed Mutagenesis Protein Protein Docking Pharmacophore Pharmacophore Modelling in SCHRÖDINGER Finding Pharmacophore Features Using MOE Open Source Tools for Pharmacophore Generation Rules of Thumb for Structure-Based Drug Design Do it Yourself Exercises Questions References

4 xvi Contents 5 Active Site-Directed Pose Prediction Programs for Efficient Filtering of Molecules Introduction A Practice Tutorial for Predicting Active Site Using SiteMap A Practice Tutorial for Active Site Prediction Using MOE Free Online Tools for Active Site Prediction Homology Modelling A Practice Tutorial for Homology Modelling Model Validation Using Online Servers Receptor-Based Pharmacophore Studies on Active Site Structural Features Application of Active Site Features in Chemoinformatics Thumb Rules for Active Site Identification and Homology Modelling Do it Yourself Exercises Questions References Representation, Fingerprinting, and Modelling of Chemical Reactions Introduction Reaction Representation in Computers Computational Methods in Reaction Modelling Empirical and Semiempirical Methods Molecular Mechanics Methods Molecular Dynamics Methods Statistical Mechanics and Thermodynamics The Quantum Mechanical/molecular Mechanical Approach Modelling the Transition State of Reactions TS Modelling of Organic Transformations Name Reactions A Practice Tutorial for Transition State and Intrinsic Reaction Coordinate Modelling A Practice Tutorial Using Maestro Jaguar A Practice Tutorial Using Spartan Reaction-Searching Approaches and Tools Chemical Ontologies Approach for Reaction Searching Reaction Searching Using Fingerprints-Based Approach Tools for Reaction Searching Reaction Databases Tools for Reaction Library Enumeration A Practice Tutorial Artificial Intelligence in Chemical Synthesis Modelling Enzymatic Reactions

5 Contents xvii 6.9 Thumb Rules for Performing Reaction Representation, Fingerprints, and Modelling Do it Yourself Questions References Predictive Methods for Organic Spectral Data Simulation Introduction Fragment-Based Drug Discovery Spectra Prediction Methods Spectra Prediction Tools Open-Source Tools GAMESS Proprietary Tools ACD/NMR Predictors Cambridgesoft Chem3D Jaguar Gaussian ADF MestreNova Spartan Spectral Databases Spectra Viewer Programs In-House Tools for Spectra Prediction Code to Generate Proton and Carbon NMR Spectrum Thumb Rules for Spectral Data Handling and Prediction Do it Yourself Questions References Chemical Text Mining for Lead Discovery What is Text Mining? Text Mining vis-a-vis Data Mining A Snippet of Java Code Using the Above URL What are the Components of Text Mining? Text-mining Methods Statistics/ML-based Approach Rule-based Approach Why Text Mining General Text-mining Tools A Practice Tutorial with an Open-source Tool R Program for Text Mining Free Tools for Text Mining Biomedical Text Mining Chemically Intelligent Text-mining Tools

6 xviii Contents 8.9 In-house Tools for Text-mining Applications for Chemoinformatics Java Code Snippet for Data Distribution Thumb Rules While Performing and Using Text-mining Results Do it Yourself Questions References Integration of Automated Workflow in Chemoinformatics for Drug Discovery What is a Workflow? Need for Workflows General Workflows in Bioinformatics General Workflows in Chemistry Domain Accelrys Pipeline Pilot IDBS Chemsense (Inforsense Suite) CDK Taverna KNIME Workflow Examples Workflow for QSAR (Anti-cancer) Schrodinger KNIME Extensions A Practice Tutorial Other KNIME Extensions MOE(CCG) ChemAxon Protein Ligand Analysis-Based Workflows for Drug Discovery A Practice Tutorial for Protein Ligand Fingerprint Generation Prolix J-ProLINE: An In-house-developed Chem-Bioinformatics Workflow Application Targetlikeness Score Databases and Tools Thumb Rules for Generating and Applying Workflows Do it Yourself Questions References Cloud Computing Infrastructure Development for Chemoinformatics What is a Portal? Need for Development of Scientific Portals Components of a Portal Examples of Portal Systems

7 Contents xix 10.5 A Practice Tutorial for Portal Creation Custom Database connection and Display Table with Paginator via portlet in Liferay Portal A Practice Tutorial for Development of Portlets for Chemoinformatics Marvin Sketch Portlet JME Portlet Jchempaint Portlet Mobile Computing Android Applications for Chemoinformatics Need of High-Performance Computing in Chemoinformatics Thumb Rules for Developing and Using Scientific Portals and Mobile Devices for Computing Do it Yourself Exercises Questions References Index

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