Computer‐Assisted Library Design
Andreas Dominik · Methods and principles in medicinal chemistry · 2006
This chapter contains sections titled: Introduction Optimizing Combinatorial Libraries A Computer-Assisted Design Strategy What is Diversity? First Examples Diversity of Drug Molecules Diversity and Similarity How Do We Compute Diversity? An Overview Descriptors Classification and Mapping Interpretation of Results: Summary Descriptors Simple Filters Physico-chemical Constants Estimation of logP Values Estimation of pK A Values Drug-Likeness The Rule of 5 Artificial Neural Networks Further Improvements of Drug-Likeness Prediction ADME and Toxicity Profiling Molecular Fingerprints Substructure Descriptors Single Atom Properties Atom Charges Atomic Lipophilicity Parameters Topological Indices Atom Indices Molecule Indices Topological Autocorrelation and Cross-correlation Coefficients Scaffold-based Similarity Descriptors from a Pharmacophore Model Stereochemistry Descriptors from the Three-Dimensional Structure Polar Surface Area (PSA) Distance Matrix Autocorrelation Coefficients Based on Atom Coordinates Based on Surface Properties Based on Potential Fields Radial Basis Function (RBF) Virtual Screening Clustering and Mapping Algorithms Distance Metric Tanimoto Coefficient Euclidean Distance Nonlinear Distance Scaling Mahalanobis Distance Dissimilarity-Based Selection Mapping-Based Selection Nonlinear Mapping Self-Organizing Maps Minimal Spanning Tree Cluster-Based Selection Hierarchical Clustering Analysis Partition-Based Selection Strategies for Compound Selection Optimization Based on Diversity of Building Blocks Advantages of Educt-Based Optimization Optimization Based on Diversity of Product Libraries Advantages of Product-Based Optimization Library Selection Evolutionary Design Circle Comparison of Descriptors and Selection Methods Topological Descriptors Descriptors Based on Three-Dimensional Structure Clustering Methods Summary Example Library of Thrombin Inhibitors Virtual Library Design Final Library Design Maximum Diversity Library Targeted Library Descriptor Sets Comparison of the Libraries Summary References