About EWCL
EWCL (Entropy-Weighted Collapse Likelihood) is a biophysics-inspired metric to estimate mutation sensitivity in protein regions.
While many models focus on sequence or evolution, EWCL models thermodynamic instability through entropy structure gradients. It is independent from traditional conservation scoring, and therefore complementary to tools like AlphaMissense or PolyPhen.
It treats entropy not as noise, but as a predictive signal for structural collapse.
Key Concepts
- Entropy as Signal: Rather than viewing entropy as noise or uncertainty, EWCL treats it as a meaningful signal that can predict regions of potential structural instability.
- Thermodynamic Approach: EWCL is grounded in biophysical principles, focusing on the thermodynamic properties that influence protein folding and stability.
- Complementary Analysis: While tools like AlphaMissense focus on evolutionary conservation, EWCL provides an orthogonal perspective based on structural physics.
- Mutation Sensitivity: By identifying regions with high entropy gradients, EWCL can predict areas where mutations are more likely to cause significant structural changes.
Applications
- Predicting mutation sensitivity in protein regions
- Identifying potential structural collapse hotspots
- Complementing sequence-based mutation analysis tools
- Guiding experimental design for protein engineering
- Understanding protein dynamics and stability
EWCL is currently in beta. We welcome feedback and collaboration from researchers interested in protein structure and dynamics.