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

Abstract

Abstract 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. CDGA was validated using controlled geometrical and chemical modifications and cross-docked and redocked poses generated for conformationally diverse native cyclodextrins, demonstrating robust and reproducible descriptor calculation despite differences in atom ordering, bond representation, host orientation, and molecular file generation, thereby enabling standardized comparison of cyclodextrin inclusion geometries, transparent reporting, benchmarking, and large-scale analysis of computational host–guest studies.

The authors' abstract, as published at the source. Journal of Chemical Information and Modeling, 2026 · DOI ↗