CageCavityCalc (C3): A Computational Tool for Calculating and Visualizing Cavities in Molecular Cages

Abstract

Organic(porous) and metal–organic cages are promising biomimetic platforms with diverse applications spanning recognition, sensing, and catalysis. The key to the emergence of these functions is the presence of well-defined inner cavities capable of binding a wide range of guest molecules and modulating their properties. However, despite the myriad cage architectures currently available, the rational design of structurally diverse and functional cages with specific host–guest properties remains challenging. Efficiently predicting such properties is critical for accelerating the discovery of novel functional cages. Herein, we introduce CageCavityCalc (C3), a Python-based tool for calculating the cavity size of molecular cages. The code is available on GitHub at https://github.com/VicenteMartiCentelles/CageCavityCalc. C3 utilizes a novel algorithm that enables the rapid calculation of cavity sizes for a wide range of molecular structures and porous systems. Moreover, C3 facilitates easy visualization of the computed cavity size alongside hydrophobic and electrostatic potentials, providing insights into host–guest interactions within the cage. Furthermore, the calculated cavity can be visualized using widely available visualization software, such as PyMol, VMD, or ChimeraX. To enhance user accessibility, a PyMol plugin has been created, allowing nonspecialists to use this tool without requiring computer programming expertise. We anticipate that the deployment of this computational tool will significantly streamline cage cavity calculations, thereby accelerating the discovery of functional cages.