Book content

Introduction to Pharmaceutical Bioinformatics

(ISBN: 978-91-979403-0-6; inquiries to info@oakleafacademic.com).

  • Preface
  • Introduction
  • Background
    • The modern pharmaceutical industry
    • Sciences dealing with drugs
    • Molecular basis of drug actions
      • Physicochemical basis for drug-target interactions
      • Drug selectivity
      • Chemical effects in drug-target interactions
      • Agonism, antagonism and inverse agonism
    • The drug in the living organism
      • Pharmacokinetics
      • Pharmacodynamics
      • Biological barriers
      • Drug absorption
      • Drug distribution
      • Drug metabolism and elimination
      • Pharmacodynamics
    • Open and closed source software
    • Cheminformatics
    • Chemometrics
    • Bioinformatics
  • Drug discovery and development
    • The drug discovery phase
      • Target identification
      • Target validation
      • Lead generation
      • High-throughput screening
      • Fragment based screening
      • Virtual screening
      • Hit-to-lead
      • Lead optimization
      • Pre-clinical development
    • Clinical trials
    • Cheminformatics and molecular modeling in drug discovery
      • Cheminformatics in drug discovery
      • Molecular modeling in drug discovery
      • Structure based drug design
      • Pharmacophore based drug design
    • Open source software for drug design
  • Bioinformatics, drugs and omics
    • Genome sequencing
    • Genotyping
      • Background to genotyping
      • Implications of genotyping in the drug area
      • Genotyping in infectious diseases
    • Polymorphisms of drug metabolism
    • Polymorphisms of drug targets
    • Polymorphisms and adverse drug effects
    • Transcriptomics
      • Methods for transcriptome analysis
      • DNA microarrays
      • Serial analysis of gene expression
      • RNA-Seq
      • Regulation of the transcriptome
      • Applications of transcriptomics
    • Proteomics
      • Basic techniques in proteomics
      • Quantitative proteomics
      • Metabolic incorporation of stable isotopes
      • Tagging with isotope-labelled tags
      • Protein-protein interactions
      • Ligand-protein interactions
      • Post-translational modifications
      • Applications of proteomics
    • Metabolomics
    • Future outlook
  • Representing molecules using computers
    • The chemical graph
      • Delocalization
      • Tautomerism
    • Connection matrices
    • Connection tables
    • Line notation systems
      • SMILES and OpenSmiles
      • SMILES: Atoms and bonds
      • SMILES: Branches and cycles
      • InChI
        • InChI: Layers
        • InChI: Atom Numbering
        • InChI: Connectivity Layer
        • InChI: Hydrogen Layer
        • InChI: Mobile hydrogens
      • InChIKey
    • File formats
      • CML FILES
    • Substructure and query representation
      • SMARTS
    • Bioclipse excursion
      • Drawing molecular structures
      • Wizards: new molecule from smiles
      • Calculating inchis and inchikeys
      • Creating a cml document and opening it in a text edi- tor
      • Substructure searching
  • Representation of 3D structures
    • Coordinate systems
      • Notational coordinates
      • Internal coordinates
    • Geometry optimization
      • Force fields
      • Semi-empirical methods
    • Conformers
    • Comparing geometries
    • Bioclipse excursion
      • Creating 3d molecular geometries.
      • Creating 3d geometries of various conformers of a single molecule.
      • Kabsch alignment in bioclipse
  • Molecular descriptors
    • Vectorial representations
    • Similarity and distance
    • Dimensionality based descriptors
      • 0D Descriptors
      • 1D Descriptors
      • 2D Descriptors
      • 3D Descriptors
      • 4D Descriptors
      • Constitutional, topological, geometrical, and electronic descriptors
    • Fingerprints
      • Substructure fingerprints
      • Comparing fingerprints
    • Grid approaches
      • CoMFA
      • GRID descriptors
      • Grid independent descriptors
    • Information contents
    • Bioclipse excursion
      • Calculating molecular descriptors
      • Calculating the descriptors
  • Sequence analysis
    • Introduction to sequence analysis
    • Representation of sequences
      • FASTA format
      • EMBL format
      • GenBank format
      • Protein data bank format
    • Sequence alignments
      • Multiple sequene alignment
      • Substitution matrices
      • Alignment software
    • Phylogenetics
    • Bioclipse excursion
      • Aligning sequences in Bioclipse
  • Macromolecular descriptors
    • Description of building blocks
      • Descriptions of amino acids
      • Description of nucleosides
    • Alignment-based descriptions
    • Alignment-independent approaches
      • Auto- and cross-covariances
      • Dipeptide compositions
      • Other approaches
    • 3D based methods
    • Bioclipse excursion
      • How to develop your own protein descriptors using Bioclipse
  • Design of experiments
    • Principles of experimental design
    • Step-by-step procedure in effective design of experiments
    • Experimental designs
      • OFAT
      • Factorial designs
      • Fractional factorial designs
      • D-optimal designs
    • Statistical molecular design
  • Data analysis
    • Introduction to data analysis
    • Nomenclature and notations
    • Models
      • Classification of mathematical models
      • Statistical models
    • Supervised learning
      • Loss function
      • Model choice and the bias-variance tradeoff
      • Linear supervised methods
        • Linear regression
        • Variable selection
        • Ridge regression
        • Partial least squares
        • Linear classification
      • Non-linear supervised methods
        • Neural networks
        • Support vector machines
        • Random forest
      • Choosing a model
        • Information criteria
        • Cross-validation
      • Model assessment
    • Unsupervised learning
      • Principal component analysis
      • Clustering
        • Hierarchical clustering
        • K-means clustering
  • Databases in pharmaceutical bioinformatics
    • Introduction to databases
    • Nucleotide databases
    • Protein databases
    • Chemistry databases
    • Interaction databases
    • Pathway databases
    • Drug target databases
    • Bibliographic databases
    • Data integration
    • Bioclipse excursion
      • Downloading sequences with Bioclipse
      • Downloading protein structures with Bioclipse
      • Query PubChem for chemical substances with Bioclipse
  • QSAR
    • Biological activities studied in QSAR and QSPR
    • Early developments of QSAR
      • Hammet constants
      • Free-Wilson approach
    • The multivariate approach to QSAR
    • Bioclipse excursion
      • QSAR modeling of peptide interactions with dengue virus NS3 protease by use of Bioclipse
  • Proteochemometrics
    • Introduction to proteochemometrics
      • Requirements for proteochemometrics
    • Comparisson of proteochemometrics with QSAR
    • Cross-terms in proteochemometrics
    • The interaction space
    • Proof of concept of proteochemometrics
      • Validation of proteochemometrics by recombinant technology
        • Validation of proteochemometrics by site-directed mutagenesis
        • Covariation in of proteochemometrics modeling
        • Discussion on proteochemometrics validation by recombinant technology
      • Validation of proteochemometrics for organic compounds
      • Validation by external predictions
    • Examples of the use of proteochemometrics
      • Retroviral proteases
      • Reverse transcriptases
      • Protein kinases
      • Major histability complexes
      • Cytochrome P450 enzymes
      • Enzyme wide and proteome wide proteochemometric models
      • Use of proteochemometrics on a few targets
    • Future perspectives of proteochemometrics
    • Bioclipse excursion
      • Proteochemometrics modeling of peptide interactions with dengue virus NS3 proteases
  • Semantic web
    • Open standards
      • RDF principles 1: URIs
      • RDF principle 2: triples
      • RDF graphs
    • File formats
      • RDF/Turtle
      • RDF/XML
      • RDFa
    • Ontologies
      • RDF schema
      • The web ontology language
    • Linked open data
    • Limitations of the semantic web
    • Conclusions
  • Appendices
    • Appendix A: Basic probability theory
    • Appendix B: Basic matrix algebra
    • Appendix C: Introduction to Bioclipse
      • Dowloading Bioclipse and getting started
      • Getting updates and features
      • The Bioclipse workbench
      • Views, editors and wizards
      • Projects
      • Bioclipse scripting langugage
    • Appendix D: Introduction to R