Outliers in SAR and QSAR: Is unusual binding mode a possible source of outliers?

Special Issue: Yvonne Martin Retirement

Abstract

A lead optimization is usually carried out by structure-activity relationship (SAR) and/or quantitative structure-activity relationship (QSAR) studies. One of the assumptions in SAR and QSAR studies is that similar analogs bind to the same binding site in a similar binding mode. One often observes that there are outliers, especially in QSAR. However, most QSAR studies are carried out focusing their attention to the development of QSAR and leave the outliers without much attention. We searched a number of ligand-bound X-ray crystal structures from the protein structure database to find evidences that could indicate a possible source of outliers in SAR or QSAR. Our results show that unusual binding mode could be a source of outliers.

Keywords

SAR QSAR Outlier Binding mode X-ray structures Source of outliers 

Notes

Acknowledgments

The author express sincere gratitude to both Professor Corwin Hansch and Dr. Albert Leo for their generous permission to use their C-QSAR database and the BioByte program Bio-Loom. The author thanks to Drs. Albert Leo and Yvonne Martin for their critical evaluation of the manuscript and valuable suggestions. The author dedicates this paper to the lifetime advisors and friends, Drs. Corwin Hansch, Albert Leo, Yvonne Martin, and Gary Grunewald.

Supplementary material

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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  1. 1.Hope Drug Discovery Research LaboratoryVernon HillsUSA

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