Revisiting van der Waals Radii: From Comprehensive Structural Analysis to Knowledge‐Based Classification of Interatomic Contacts

Weak noncovalent interactions are responsible for structure and properties of almost all supramolecular systems, such as nucleic acids, enzymes, and pharmaceutical crystals. However, the analysis of their significance and structural role is not straightforward and commonly requires model studies. Herein, we describe an efficient and universal approach for the analysis of noncovalent interactions and determination of van der Waals radii using the line‐of‐sight (LoS) concept. The LoS allows to unambiguously identify and classify the “direct” interatomic contacts in complex molecular systems. This approach not only provides an improved theoretical base to molecular “sizes” but also enables the quantitative analysis of specificity, anisotropy, and steric effects of intermolecular interactions. Seeing trees behind the forest! A method based on the line‐of‐sight concept to efficiently eliminate the background from randomly distributed contacts and analyze intermolecular interactions within diverse extended structural datasets is presented. This approach allowed to more specifically define the vdW parameters from the bulk structural data and to identify atom‐type specific vdW radii with clear physical meaning.