Measure capacity and passage separately
An atom-based clearance field records the space around the encoded atoms under a declared radius convention. Exterior-rooted connectivity structures then distinguish an internal basin from the bottleneck on an approach from outside. Definite, nominal and possible calculations expose when uncertainty changes the answer.
The calculation distinguishes cavity capacity, an internal merge and connection to the exterior. Those are different events. Its uncertainty handling can retain an unresolved answer when the admitted bounds do not support a decision.
CAVER already analyzes transport paths and their changing bottlenecks across molecular-dynamics snapshots. The additional BioTwin question is how an explicit uncertainty model affects the geometric decision.
| Question | Familiar approach | BioTwin | Why it matters |
|---|---|---|---|
| Can it fit? | Pocket geometry or a docked pose examines the available internal space. | Computes geometric fit separately from entry clearance. | A plausible bound pose does not settle the approach route. |
| Can it enter? | CAVER characterizes tunnels, bottleneck radii and their variation over trajectories. | Uses exterior-rooted clearance structures to assess access to a basin. | The entrance can rule out a proposal even when the cavity is large enough. |
| Does uncertainty change the answer? | A trajectory or parameter sweep reveals variation in the sampled cases. | Keeps definite, nominal and possible outcomes relative to admitted bounds. | An unresolved result identifies where the geometry or numerical assumptions need refinement. |
This is a scoped geometric method, not a certified biological-access claim or a demonstrated advantage over CAVER.
Test the route before designing around the pocket
A computational control demonstrated the important case of a probe that fits inside a cavity but cannot enter under the geometric model. Applied after cryptic-pocket localization, this analysis can challenge an attractive opening before a team designs chemistry around it. Adding ensemble weighting could test whether access depends on a rare conformation; that combined biological interpretation needs separate validation.
Read “certified” at the scale of the model
The certificate concerns the encoded geometry and supported numerical assumptions. Atomic radii, hydrogens, alternate locations, ligand shape and structural uncertainty can change the result. Several error terms remain unmeasured, and refinement convergence has not been established for every access calculation. Protein motion, solvent transport and experimental binding lie beyond the geometric certificate.
The next question is how this geometry relates to a relevant protein state. Protein State Control explains the additional population, capture and functional evidence that an intervention requires.
- Connect geometry to the intervention objective Explore Protein State Control