Docking Methods for Structure-Based Library Design

The drug discovery process mainly relies on the experimental high-throughput screening of huge compound libraries in their pursuit of new active compounds. However, spiraling research and development costs and unimpressive success rates have driven the development of more rational, efficient, and cost-effective methods. With the increasing availability of protein structural information, advancement in computational algorithms, and faster computing resources, in silico docking-based methods are increasingly used to design smaller and focused compound libraries in order to reduce screening efforts and costs and at the same time identify active compounds with a better chance of progressing through the optimization stages. This chapter is a primer on the various docking-based methods developed for the purpose of structure-based library design. Our aim is to elucidate some basic terms related to the docking technique and explain the methodology behind several docking-based library design methods. This chapter also aims to guide the novice computational practitioner by laying out the general steps involved for such an exercise. Selected successful case studies conclude this chapter.