Stacking Interactions of Druglike Heterocycles with Nucleobases.

ABSTRACT: Stacking interactions contribute significantly to the interaction of small molecules with RNA, and harnessing the power of these interactions will likely prove important in the development of RNA-targeting inhibitors. To this end, we present a comprehensive computational analysis of stacking interactions between a set of 54 druglike heterocycles and the natural nucleobases. We first show that heterocycle choice can tune the strength of stacking interactions with nucleobases over a large range and that heterocycles favor stacked geometries that cluster around a discrete set of stacking loci characteristic of each nucleobase. Symmetry-adapted perturbation theory results indicate that the strengths of these interactions are modulated primarily by electrostatic and dispersion effects. Based on

SUBMITTER: Conner AV 

PROVIDER: S-EPMC12004538 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature