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The R-5′-methyl group (modeled) juts into a hydrophilic environment and will interfere (flash) with phosphate hydration (water molecules are cyan and purple spheres) as observed in the 0.83 Å crystal structure of an A-form DNA.19 The shorter distance between O1P oxygens on the edge of the major groove can typically be bridged by a single water (purple), whereas the wider spacing between O2P oxygens requires 2-water bridges (cyan).
