Design and Application of Fragment Libraries for Protein Crystallography: Computational Approaches to Compound Selection

摘要

The x-ray diffraction analysis of protein crystals soaked in libraries of fragment compounds is able to identify those small compounds that specifically bind to critical sites on the protein. This crystal structure data may be used in the subsequent design of focused scaffold libraries for early lead discovery. By applying simple computational tools to search through the several million off-the-shelf screening compounds currently available it is possible to implement fragment screening methodologies in academic and small biotechnology laboratory environments.