Machine learning shows torsion angle preferences in left-handed and right-handed quadruplex DNAs

Abstract

Left-handed G quadruplexes (LHG4) have been recently discovered as a new class of G quadruplexes. The biological functions of LHG4s are still unknown, but they share a striking resemblance to Z-DNA in their helicity and jagged phosphate backbone. To further understand structural features of the LHG4s that define their left handedness, we have employed human-interpretable machine-learning methods to classify right- and left-handed G4s purely based on torsional angle analysis. Our results reveal the importance of the α, β, δ, and χ angles in left-handed structuring across both Z-DNAs and LHG4s. Our analysis may serve as the first step to understanding the conditions of formation for LHG4s and their potential biological relevance.