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Updated: Mar 21, 2026

Incorporating Target Protein Structure Flexibility and Dynamics in Computational Drug Discovery Using Ensemble-Based Docking Analysis
Published on: June 20, 2025
Best Practices in Structural Ensemble Analysis: Avoiding Pitfalls, Interpreting Results, and Automating Workflows
Melanie Schneider1,2, José Antonio Marquez2, Andrew R Leach1
1European Molecular Biology Laboratory, EMBL-EBI, Wellcome Genome Campus, Hinxton, United Kingdom.
Abstract:
Structural ensemble analysis is critical for understanding protein flexibility, function, and interactions. EnsembleFlex provides a streamlined framework for dual-scale (backbone-only and all-atom) flexibility analysis by integrating both data-driven and predictive approaches. This article outlines best practices for analyzing protein ensembles, with detailed guidance on avoiding common pitfalls, interpreting outputs from both backbone-only and all-atom assessments (including RMSD, RMSF, PCA, and UMAP plots), and automating workflows for reproducibility. The framework is designed to require minimal user adjustments, allowing researchers to adapt the protocol to various datasets and research objectives with ease. © 2026 The Author(s). Current Protocols published by Wiley Periodicals LLC. Basic Protocol: Best practices for structural ensemble analysis.
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