The Challenge
KRAS mutations drive approximately 25% of all human cancers, with the G12D mutation being one of the most prevalent oncogenic variants. Despite decades of research, KRAS has remained largely "undruggable" due to its smooth surface and lack of traditional binding pockets. However, recent advances in molecular dynamics (MD) simulations suggest that cryptic pockets—transient binding sites that emerge during protein dynamics—may offer new therapeutic opportunities.
In this case study, we present our approach to discovering cryptic binding pockets in the active KRAS G12D mutant using multi-microsecond molecular dynamics simulations enhanced with advanced sampling techniques.
Key Objectives
- 🔸 Multi-microsecond sampling to capture rare conformational states and transient pocket formation
- 🔸 Enhanced sampling techniques with parallel replica workflows across multiple high-performance GPUs
- 🔸 Cryptic pocket identification using geometric analysis and binding site prediction
- 🔸 Therapeutic target validation through virtual screening and binding affinity calculations
Full Case Study Coming Soon!
Interested in Cryptic Pocket Discovery?
Our enhanced sampling protocols can be applied to other challenging drug targets. Contact us to discuss how we can help advance your research.
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