These authors contributed equally to this work.
Using Ligand-Mapping Simulations to Design a Ligand Selectively Targeting a Cryptic Surface Pocket of Polo-Like Kinase 1†
Article first published online: 7 SEP 2012
Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Angewandte Chemie International Edition
Volume 51, Issue 40, pages 10078–10081, October 1, 2012
How to Cite
Tan, Y. S., Śledź, P., Lang, S., Stubbs, C. J., Spring, D. R., Abell, C. and Best, R. B. (2012), Using Ligand-Mapping Simulations to Design a Ligand Selectively Targeting a Cryptic Surface Pocket of Polo-Like Kinase 1 . Angew. Chem. Int. Ed., 51: 10078–10081. doi: 10.1002/anie.201205676
We are grateful for funding from the Agency for Science, Technology and Research (Y.S.T.), the Wellcome Trust, the Gates Cambridge Trust, St. Edmund’s College (P.Ś.) and DAAD (S.L.). R.B.B. is supported by a Royal Society University Research Fellowship. We thank Dr. Marko Hyvönen for assistance with the structural biology, Dr. Chandra Verma for helpful discussions.
- Issue published online: 26 SEP 2012
- Article first published online: 7 SEP 2012
- Manuscript Received: 17 JUL 2012
- Funded Access
- Agency for Science, Technology and Research
- Wellcome Trust
- Gates Cambridge Trust
- St. Edmund’s College
- drug design;
- molecular dynamics;
- molecular recognition;
- protein dynamics;
- protein–protein interactions
An explicit solvent ligand-mapping approach was used to reveal an otherwise hidden hydrophobic pocket in polo-like kinase 1 (Plk1). It predicted a novel ligand binding mode that was used for the design of a new ligand with high affinity for Plk1. X-ray crystallography confirmed that the binding was specific to the intended pocket.