Expanding Balloons: Robust Computational Method for Determining Supramolecular Cage Cavity Morphology Based on the “Inflating Balloon” Metaphor

Supramolecular cages with adjustable internal cavities are widely used as host systems for chemical sensing, catalysis, drug release, and host–guest chemistry. The accurate calculation and visualization of these cavity morphologies are crucial for analyzing and understanding supramolecular cages. Most existing cavity computation tools are suitable for small cavities with few voids, such as those found in natural protein pockets. However, these tools have insufficient accuracy and robustness when applied to larger cavities in supramolecular cages. Drawing inspiration from the concept of deformable container expansion, this paper presents a computational method for determining the morphology of supramolecular cage cavities based on the “inflating balloon” metaphor (CMCC). First, through experimental examination of supramolecular cages, we take the center of mass as the origin of expansion and create probe vertices via subdivision surfaces. Subsequently, we introduce the “probe vertex diffusion algorithm”, which facilitates the generation of the overall cavity morphology by simulating the inflating-balloon process. Through comparative analysis and validation of the experimental results, CMCC is found to have advantages in terms of accuracy and robustness for cavity computation compared with existing primary computational tools for supramolecular cage cavities.

具有可调节内部空腔的超分子笼（supramolecular cages）作为主体体系，被广泛应用于化学传感、催化、药物释放以及主客体化学领域。精准计算并可视化这类空腔的形貌，对于分析与认知超分子笼至关重要。当前主流的空腔计算工具多适用于天然蛋白质口袋这类空隙较少的小型空腔，但将其用于超分子笼的大型空腔时，计算精度与鲁棒性均存在不足。受可变形容器膨胀理念的启发，本文提出一种基于“充气气球”隐喻的超分子笼空腔形貌计算方法（CMCC）。首先，针对超分子笼开展实验表征，以其质心作为膨胀原点，并通过细分曲面生成探针顶点；随后引入“探针顶点扩散算法”，通过模拟充气气球的膨胀过程，实现整体空腔形貌的生成。通过对比分析与实验结果验证，相较于现有主流超分子笼空腔计算工具，CMCC在空腔计算的精度与鲁棒性方面均表现更优。