A compound library is a collection of real stored chemicals and/or virtual chemical compounds. The compound library or chemical library can contain stored chemicals each of them has associated data with information such as the chemical structure, purity, quantity, and physiochemical characteristics of the compound. The virtual compound libraries consist of 2D or 3D representations of chemical compounds that are used for diverse purposes using computational methods.
The logical designs of both library types are often similar to one another, and the two methods — experimental (for real compound libraries) and computational (for virtual compound libraries) are often complement one another in drug discovery development process.
What is a purpose of a compound library?
Compound libraries usually used for drug discovery high-throughput screening, a process consisting of testing a large number of chemicals against some assays and/or targets.
Both real and virtual compound libraries are commonly run in parallel in drug discovery campaigns with the results of one compared to the other. The main purpose is to design libraries for promising new drug leads. 20 years ago, the first libraries typically included huge amounts of small-molecule structures; today compound libraries design is more sophisticated than in the past and centers around the methods used for choosing compound membership. The choice of compounds is often based on two widely used design strategies: diversity oriented design and target oriented design. The goal of diversity oriented design strategy is to generate libraries with a highly diverse set of chemical compounds based for example on skeletal diversity, a strategy where the scaffold elements of chemical compounds are chosen to maximize their variation in 3D structure, electrostatics, or molecular properties. A molecular property diversity method include hydrogen bond donors/acceptors, polarizable groups, charge distributions, hydrophobic and lipophobic fragments, and numerous other properties. The diversity of the libraries resulting from these methods is often measured using statistical techniques, such as cluster and principal components analysis. In contrast to diversity, target oriented design seeks to create libraries that are focused around specific chemotypes, molecular species, or classes of compounds. Compound libraries with target oriented design results in focused libraries with a limited number of well-defined structures. To generate focused libraries 3D shape, 3D electrostatics, pharmacophore models, molecular descriptors, and target active sites are used.
Regardless of diversity or target oriented design chemical compounds need to satisfy a variety of constraints before they become marketable drugs, for instance, Lipinski’s rules place limits on molecular weight, the number of hydrogen bond donors and acceptors, the number of rotatable bonds, and solubility. Applying Lipinski’s rules in library design acts as a molecular property filter, you can effectively restrict the set of compounds to those with drug-like characteristics.