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Updated: May 27, 2026

Incorporating Target Protein Structure Flexibility and Dynamics in Computational Drug Discovery Using Ensemble-Based Docking Analysis
Published on: June 20, 2025
Understanding biomolecular motion, recognition, and allostery by use of conformational ensembles
R Bryn Fenwick1, Santi Esteban-Martín, Xavier Salvatella
1Joint BSC-IRB Research Programme in Computational Biology, Institute for Research in Biomedicine, IRB Barcelona, Spain.
Abstract:
We review the role conformational ensembles can play in the analysis of biomolecular dynamics, molecular recognition, and allostery. We introduce currently available methods for generating ensembles of biomolecules and illustrate their application with relevant examples from the literature. We show how, for binding, conformational ensembles provide a way of distinguishing the competing models of induced fit and conformational selection. For allostery we review the classic models and show how conformational ensembles can play a role in unravelling the intricate pathways of communication that enable allostery to occur. Finally, we discuss the limitations of conformational ensembles and highlight some potential applications for the future.
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