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Using Ligand‐Mapping Simulations to Design a Ligand Selectively Targeting a Cryptic Surface Pocket of Polo‐Like Kinase 1
Author(s) -
Tan Yaw Sing,
Śledź Paweł,
Lang Steffen,
Stubbs Christopher J.,
Spring David R.,
Abell Chris,
Best Robert B.
Publication year - 2012
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201205676
Subject(s) - ligand (biochemistry) , polo like kinase , plk1 , chemistry , kinase , biophysics , combinatorial chemistry , stereochemistry , biochemistry , biology , receptor , cell cycle , cell
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.