To demonstrate the utility of the C3 algorithm, we tested it in 23 algorithm using MoloVol with a large probe radius of 3 Å, a small probe radius of 1.0 Å, and grid resolution of 0.5 Å, (f) Calculation reported in Ref. 71 using SwissPDBViewer with a probe radius of 1.4 Å. Figure An important feature of our algorithm is its compatibility with MD simulations, enabling the assessment of dynamic changes in volume over time. To illustrate this, we analyzed the MD trajectory of the [Pd4L6] 12+ , Cage 3, using VOIDOO software that employs the rolling probe algorithm and our C3 software. This comparison highlighted the advantages of the C3 angle-based algorithm over the rolling one-probe algorithm (Figure ). The calculation of the cavity volume with VOIDOO with a standard probe size of radius 1.4 Å exhibited significant variations in the calculated volume over time of ca. 30% (Vcavity = 307 ± 97 Å 3 ), primarily due to over-/underestimating the cavity volume in several frames, giving 0 values in some instances (see Figure blue line). While increasing the probe size (radius = 2.4 Å) mitigated this issue by preventing the probe from escaping from the cavity, it led to a much smaller cavity size with a ca. 60% variation over time (Vcavity = 57 ± 35 Å 3 , see Figure green line). In contrast, our C3 algorithm with default parameters provided a more robust and well-defined cavity with a volume variation over time of ca. 10% (Vcavity = 323 ± 31 Å 3 , see Figure orange line). These results highlight the robustness of the angle-base algorithm of C3 for analyzing MD trajectories.