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Updated: Jan 3, 2026

Incorporating Target Protein Structure Flexibility and Dynamics in Computational Drug Discovery Using Ensemble-Based Docking Analysis
Published on: June 20, 2025
Multi-scale modeling of drug binding kinetics to predict drug efficacy
Fabrizio Clarelli1, Jingyi Liang1, Antal Martinecz1
1Department of Pharmacy, Faculty of Health Sciences, UiT The Arctic University of Norway, 9037, Tromsø, Norway.
Abstract:
Optimizing drug therapies for any disease requires a solid understanding of pharmacokinetics (the drug concentration at a given time point in different body compartments) and pharmacodynamics (the effect a drug has at a given concentration). Mathematical models are frequently used to infer drug concentrations over time based on infrequent sampling and/or in inaccessible body compartments. Models are also used to translate drug action from in vitro to in vivo conditions or from animal models to human patients. Recently, mathematical models that incorporate drug-target binding and subsequent downstream responses have been shown to advance our understanding and increase predictive power of drug efficacy predictions. We here discuss current approaches of modeling drug binding kinetics that aim at improving model-based drug development in the future. This in turn might aid in reducing the large number of failed clinical trials.
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