CDGA: A Host-Based Alignment and Descriptor Analysis Tool for Cyclodextrin Inclusion Complexes

Computational studies of cyclodextrin inclusion complexes are widespread; however, quantitative comparison of host–guest geometries remains difficult because native cyclodextrins are cyclic and pseudosymmetric, with chemically equivalent glucose units and no unique structural anchor for conventional atom-to-atom mapping. Consequently, RMSD values, guest orientations, and pose comparisons may depend on arbitrary atom numbering, molecular file representation, or software-specific alignment procedures rather than on genuine structural differences.

To address this limitation, we developed CDGA, the Cyclodextrin Guest Analysis tool, an open-source KNIME-based tool for quantitative analysis of cyclodextrin host–guest complexes comprising CDGA Align for host-based alignment and CDGA NoAlign for analysis directly from their original coordinates; both workflows identify host and guest fragments, perform chemically meaningful atom mapping, and calculate standardized descriptors including guest depth, guest orientation, guest principal-axis angle, and heavy-atom RMSD, while an additional host module characterizes host geometry.