Schematic representation of the TAL-DNA interface.

<p>(<b>A</b>) Cartoon representation of one single repeat interacting with DNA. The <i>oxyanion clip</i> (G14, K16 and Q17) interacts with the phosphate group of the <i>(i-1)^th</i> base, thus fixing the position of the X13 side-chain with respect to the <i>i^th</i> base and freezing its structural fluctuation. Dashed circles indicate the interaction radii of different X13 residues, sorted by side-chain size: the inner circle corresponds to G13/*13, while the others are represented by the outer circle. Only loci α, β and γ are sampled by the side-chains of X13, resulting in incomplete molecular differentiation. (<b>B</b>) Pharmacophore-like model for the nucleobases discussed in the text (left). Dots represent sites with variable properties across nucleobases; colours are used to highlight the characteristics of the substituents: green for pyridine-like (H-bond acceptor) nitrogen atoms, blue for pyrrole-like and amine (H-bond donor) nitrogen atoms, grey for methyl groups, and red for carbonyl oxygen atoms. On the right, relative molecular electrostatic potential (MEP) maps for the corresponding nucleobases are reported. Calculations were performed at the QM level on methyl-capped purines (N9) and pyrimidines (N1) (red = −5.0 k_BT/e, blue = 5.0 k_BT/e, isovalue 4.0 E⁻⁴).