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Updated: Jun 2, 2026

Incorporating Target Protein Structure Flexibility and Dynamics in Computational Drug Discovery Using Ensemble-Based Docking Analysis
Published on: June 20, 2025
Utility of protein structures in overcoming ADMET-related issues of drug-like compounds
Friederike Stoll1, Andreas H Göller, Alexander Hillisch
1Bayer HealthCare AG, Global Drug Discovery, Medicinal Chemistry, Wuppertal, Germany. alexander.hillisch@bayer.com
Abstract:
The number of solved X-ray structures of proteins relevant for ADMET processes of drug molecules has increased remarkably over recent years. In principle, this development offers the possibility to complement the quantitative structure-property relationship (QSPR)-dominated repertoire of in silico ADMET methods with protein-structure-based approaches. However, the complex nature and the weak nonspecific ligand-binding properties of ADMET proteins take structural biology methods and current docking programs to the limit. In this review we discuss the utility of protein-structure-based design and docking approaches aimed at overcoming issues related to plasma protein binding, active transport via P-glycoprotein, hERG channel mediated cardiotoxicity and cytochrome P450 inhibition, metabolism and induction.
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