Chapter 9 Molecular Similarity: Advances in Methods, Applications and Validations in Virtual Screening and QSAR

This chapter discusses recent developments in some of the areas that exploit the molecular similarity principle, novel approaches to capture molecular properties by the use of novel descriptors, focuses on a crucial aspect of computational models—their validity, and discusses additional ways to examine data available, such as those from high-throughput screening (HTS) campaigns and to gain more knowledge from this data. The chapter also presents some of the recent applications of methods discussed focusing on the successes of virtual screening applications, database clustering and comparisons (such as drug- and in-house-likeness), and the recent large-scale validations of docking and scoring programs. While a great number of descriptors and modeling methods has been proposed until today, the recent trend toward proper model validation is very much appreciated. Although some of their limitations are surely because of underlying principles and limitations of fundamental concepts, others will certainly be eliminated in the future.