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Protein Cryptic Pocket Detection

The identification and exploitation of binding sites in protein structures often represent a pivotal step in designing effective therapeutics. Sites that are rarely or never observed in experimental structures, yet remain druggable, are referred to as cryptic pockets. These pockets offer novel opportunities for modulating the activity of a target protein and are particularly valuable in crafting isoform-selective ligands when the structure of the substrate-binding site remains consistent across different variants of the target protein.

Through the use of state-of-the-art enhanced sampling molecular dynamics simulations, OpenEye's Cryptic Pocket Detection tools empowers users to thoroughly explore a protein's conformational space, potentially revealing one or more cryptic pockets. Customized visual and quantitative analysis of the results can yield valuable insights into the presence and potential druggability of these pockets.

Contact us to learn how you can gain new therapeutic opportunities using OpenEye's Cryptic Pocket Detection.

Cryptic Pocket CAK Exposon Analysis Static Image
Cryptic Pocket Detection reveals an additional pocket in CAK using Exposon analysis.


  • Performance. Fast and efficient computation with Weighted Ensemble MD

  • Turn-key. Fully automated workflows in four steps

  • Flexible. Handles single and mixed solvent simulations

  • Versatile. Multiple pocket detection methods are provided

Uncover hidden features in protein structures

Transitioning from static structures to dynamic insights is a critical aspect of computational chemistry.

OpenEye provides users with automated workflows to explore hidden putative ligand binding sites for challenging protein targets. Users can:

  1. Prepare and execute Weighted Ensemble (WE) Molecular Dynamics (MD) simulations in a single or mixed solvent.
  2. Conduct pocket detection analysis to identify potential cryptic pocket sites.

With OpenEye's Weighted Ensemble MD and Cryptic Pocket Detection on the Orion® Molecular Design Platform, scientists can run calculations across hundreds or even thousands of GPUs in the cloud, saving valuable discovery time. 

Image shows an example of using dynamic probe binding analysis method to identify cryptic pockets in K-Ras protein.
Cryptic_Pocket_ICEC0942-binding site
OpenEye's Cryptic Pocket workflow provides users with multiple pocket detection methods.

OpenEye’s tools for detecting these cryptic pockets helps you uncover alternative binding sites that are not apparent from the protein's primary function or known active sites. The identification of such cryptic pockets can lead to the discovery of new therapeutic opportunities and the design of novel drugs.

Learn More

OpenEye's Cryptic Pocket Detection can help you minimize the risk of off-target activity and undesired side effects, and thus save costs by reducing failure rates.

Download OpenEye Science Brief on Enhanced Sampling of Protein Conformations for Cryptic Pocket Detection

Watch OpenEye's recorded webinar December 2023 for Dr. Neha Vithani's presentation on Automated Identification of Cryptic Pockets for Drug Discovery. 


  1. Cooperative Changes in Solvent Exposure Identify Cryptic Pockets, Switches, and Allosteric Coupling. Porter, J. R.; Moeder K. E.; Sibbald C. A.; Zimmerman M. I.; Hart K. M.; Greenberg M. J.; Bowman G. R., Biophys J. 2019, 116(5), 818-830. doi: 10.1016/j.bpj.2018.11.3144. Epub 2019 Jan 25. PMID: 30744991; PMCID: PMC6400826.



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