[Frontiers in Bioscience 16, 2289-2306, June 1, 2011]

Protein-Ligand docking

Giovanni Bottegoni

Department of Drug Discovery and Development, Istituto Italiano di Tecnologia, via Morego n.30 Genova, 16163, Italy

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Protein-ligand docking flowchart
3.1. Receptor structure selection
3.2. Binding pocket representation
3.3. Binding pocket composition
3.4. Ligand conformational search
3.4.1. Deterministic algorithms
3.4.2. Stochastic alogorithm
3.4.3. Simulation methods
3.5. Receptor flexibility
3.5.1. Indirect methods
3.5.2. Local variants generation
3.5.3. Multiple receptor conformations docking
3.6. Scoring
3.6.1. Force-field-based scoring functions
3.6.2. Empirical scoring functions
3.6.3. Knowledge-based scoring functions
3.6.4. Consensus scoring
4. Compare docking protocols
5. Future perspectives
6. Conclusions
7. References

1. ABSTRACT

Ligand-docking is an established computational technique universally applied in structure-based drug design. Since the first attempts carried out in the early '80s to predict the three-dimensional conformation of a protein-ligand bound complex, this methodology has evolved constantly and it is presently implemented in many different ways. The present study aims at explaining the standard protein-ligand docking protocol, together with its main advantages and drawbacks. Milestone reports and future directions are reported and discussed as well.