gaps and channels between ligands, parametrizing unique cavity space compared to macrocyclic probes. Substituents bound to probes can also determine how small of space is accessible to the probe, and consequently the amount of detail in the resultant pocket information. Probes with H and F substituents from literature probes were compared as test cases. Smaller substituents (H) allow for exploration of space closer to the surrounding structure, resulting in a larger pocket on average. VCAVITY computed by probes CycH_12 and CycF_12 show poor correlation at low VCAVITY, indicating that they are disparately parametrizing highly confined cavities (Figure ). The smaller CycH_12 substituents increase flexibility of the probe, allowing it to explore tighter spaces more completely.