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Global fitting of our hydrodynamic and scattering data to a worm-like chain (WLC) model indicates that these multimeric G4 structures are semi-flexible, with a persistence length of ∼34 Å. Investigations of its flexibility using MD simulations reveal stacking, unstacking, and coiling movements, which yield unique sites for drug targeting.Thymine DNA glycosylase (TDG), as a repair enzyme, plays essential roles in maintaining the genome integrity by correcting several mismatched/damaged nucleobases. TDG acquires an efficient strategy to sea