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Statistical analysis of EGFR structures’ performance in virtual screening

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Abstract

In this work the ability of EGFR structures to distinguish true inhibitors from decoys in docking and MM-PBSA is assessed by statistical procedures. The docking performance depends critically on the receptor conformation and bound state. The enrichment of known inhibitors is well correlated with the difference between EGFR structures rather than the bound-ligand property. The optimal structures for virtual screening can be selected based purely on the complex information. And the mixed combination of distinct EGFR conformations is recommended for ensemble docking. In MM-PBSA, a variety of EGFR structures have identically good performance in the scoring and ranking of known inhibitors, indicating that the choice of the receptor structure has little effect on the screening.

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Acknowledgments

This work was supported by The Hormel Foundation and National Institutes of Health Grants CA172457, CA166011 and R37 CA081064.

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    Authors and Affiliations

    1. The Hormel Institute, University of Minnesota, Austin, MN, 55912, USA

      Yan Li & Zigang Dong

    2. Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450001, Henan, China

      Xiang Li

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    1. Yan Li
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    2. Xiang Li
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    3. Zigang Dong
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    Correspondence to Yan Li or Zigang Dong.

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    Yan Li and Xiang Li have contributed equally to this work.

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    Li, Y., Li, X. & Dong, Z. Statistical analysis of EGFR structures’ performance in virtual screening . J Comput Aided Mol Des 29, 1045–1055 (2015). https://doi.org/10.1007/s10822-015-9877-9

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