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Updated: Mar 26, 2026

Incorporating Target Protein Structure Flexibility and Dynamics in Computational Drug Discovery Using Ensemble-Based Docking Analysis
Published on: June 20, 2025
Drugging specific conformational states of GPCRs: challenges and opportunities for computational chemistry
Maria Martí-Solano1, Denis Schmidt2, Peter Kolb2
1Research Programme on Biomedical Informatics, Department of Experimental and Health Sciences, Pompeu Fabra University, Hospital del Mar Medical Research Institute, Dr Aiguader 88, Barcelona 08003, Spain.
Abstract:
Current advances in structural biology for membrane proteins support the existence of multiple Gprotein-coupled receptor (GPCR) conformations. These conformations can be associated to particular receptor states with definite coupling and signaling capacities. Drugging such receptor states represents an opportunity to discover a new generation of GPCR drugs with unprecedented specificity. However, exploiting recently available structural information to develop these drugs is still challenging. In this context, computational structure-based approaches can inform such drug development. In this review, we examine the potential of these approaches and the challenges they will need to overcome to guide the rational discovery of drugs targeting specific GPCR states.
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