Title

Pre-docking filter for protein and ligand 3D structures

Authors

Alisa Wilantho¹, Sissades Tongsima¹ and Ekachai Jenwitheesuk^{1, *}

Affiliation

1National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, 113 Thailand Science Park, Phahonyothin Road, Klong 1, Klongluang, Pathumtani 12120, Thailand

Email

 ekachai@biotec.or.th; * Corresponding author

Article Type

Hypothesis

Date

received November 15, 2008; accepted December 01, 2008; published December 31, 2008

Abstract

Virtual drug screening using protein-ligand docking techniques is a time-consuming process, which requires high computational power for binding affinity calculation. There are millions of chemical compounds available for docking. Eliminating compounds that are unlikely to exhibit high binding affinity from the screening set should speed-up the virtual drug screening procedure. We performed docking of 6353 ligands against twenty-one protein X-ray crystal structures. The docked ligands were ranked according to their calculated binding affinities, from which the top five hundred and the bottom five hundred were selected. We found that the volume and number of rotatable bonds of the top five hundred docked ligands are similar to those found in the crystal structures and corresponded with the volume of the binding sites. In contrast, the bottom five hundred set contains ligands that are either too large to enter the binding site, or too small to bind with high specificity and affinity to the binding site. A pre-docking filter that takes into account shapes and volumes of the binding sites as well as ligand volumes and flexibilities can filter out low binding affinity ligands from the screening sets. Thus, the virtual drug screening procedure speed is increased.

Keywords

virtual drug screening; ligand volume; protein binding site; docking filter; binding affinity

Citation

Wilantho et al., Bioinformation 3(5): 189-193 (2008)

Edited by

P. Kangueane

ISSN

0973-2063

Publisher

Biomedical Informatics

License

This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.