[Frontiers in Bioscience 16, 1276-1290, January 1, 2011]

Theoretical and computational approaches to ligand-based drug discovery

Angelo D. Favia

Istituto Italiano di Tecnologia (IIT), Drug Discovery and Development, via Morego 30, 16163 Genoa, Italy


1. Abstract
2. Introduction
2.1. Ligand-based drug design
2.2. Historical perspective
2.3. Preamble
3. Theoretical background
3.1. Five steps to 3D QSAR
3.1.1. Structural alignment of molecules
3.1.2. Generation of data
3.1.3. Mining of data
3.1.4. Validation of the model
3.1.5. Back to chemistry
3.2. 3D pharmacophore mapping
4. Advantages and disadvantages of ligand-based approaches
5. Conclusions and perspective
6. Acknowledgments
7. References


The basic idea behind ligand-based approaches is that the analysis of sets of molecules with experimentally determined activities can highlight those chemical features responsible for the activity changes. Historically, such approaches have been devised before structure-based methods. Nowadays, despite the ever increasing availability of experimentally determined structures, ligand-based approaches still play a major role in drug design either alone or in conjunction with structure-based efforts. This manuscript aims to provide a general overview of the main computational approaches in ligand-based drug discovery, particularly 3D QSAR methods, along with relevant references to the literature.