Multiscale simulation approaches to modeling drug-protein binding
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Updated: Dec 27, 2025

Incorporating Target Protein Structure Flexibility and Dynamics in Computational Drug Discovery Using Ensemble-Based Docking Analysis
Published on: June 20, 2025
Benjamin R Jagger1, Sarah E Kochanek1, Susanta Haldar2
1Department of Chemistry and Biochemistry, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, United States.
Abstract:
Simulations can provide detailed insight into the molecular processes involved in drug action, such as protein-ligand binding, and can therefore be a valuable tool for drug design and development. Processes with a large range of length and timescales may be involved, and understanding these different scales typically requires different types of simulation methodology. Ideally, simulations should be able to connect across scales, to analyze and predict how changes at one scale can influence another. Multiscale simulation methods, which combine different levels of treatment, are an emerging frontier with great potential in this area. Here we review multiscale frameworks of various types, and selected applications to biomolecular systems with a focus on drug-ligand binding.
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