Automated docking for novel drug discovery

Abstract

Introduction: The volume of three-dimensional structural information of macromolecules and the number of computational tools to predict binding modes and affinities of molecular complexes are increasing daily. Molecular docking is a rational structural approach employed to predict thermodynamic parameters based on molecular recognition between two or more molecules. In addition, docking studies have become very important for therapeutic applications in modern structure-based drug design because this computational tool uses few economic resources. However, they omit many biological conditions that critically influence small and macromolecular structural motions. To mimic physiological conditions, it is necessary to consider other environmental factors, such as the presence of water molecules and the flexibility of ligands and side chain residues of proteins. Furthermore, molecular dynamics simulations have been coupled with docking procedures to expand the boundaries and obtain more reliable information.

Areas covered: In this article, we review current advances in protein-small molecule docking and possible future directions.

Expert opinion: Docking studies include many conformations to predict binding free energies (scoring functions) and to search (scoring sampling) for the most representative binding conformations. Therefore, several biological properties, from side chain residues to complete protein motions, have been included in docking studies to improve theoretical predictions.

Keywords::

• docking
• molecular dynamics simulations
• protein target
• small ligands

Acknowledgements

M Bello and M Martínez-Archundia are supported by a fellowship from Consejo Nacional de Ciencia y Tecnología (CONACYT). The authors also acknowledge support through grants from the Instituto de Ciencia y Tecnología del Distrito Federal (ICyTDF), grant identifier PIRIVE09-9, PIFI-SIP-COFAA/IPN projects SIP (20130379) and CONACYT grant CB132353.

Declaration of interest

The authors state no conflict of interest and have received no payment in preparation of this manuscript.

Notes

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