Supplementary Data  Figure S1. The relative positions between the side-chains of residues in Arc and the DNA. (A) Front view, in one chain of the Arc dimer, three master residues Gln9 (orange), Asn11 (red) and Arg13 (blue) interact with DNA major groove; (B) Side view, Phe10 (purple) and Leu12 (cyan) are not in direct contact with DNA, pointing opposite direction to the master residues.

Figure S2. The overall structural fluctuations for the wild-type and mutant based on Cα atoms of residues 6-46. (A) unbound Arc dimer; (B) bound Arc dimer.

Figure S3. The angle distributions of side-chain rotamers of master residues. A-C: Unbound structures, D-F: Bound structures. The side-chains of the wild-type Arc are more flexible in unbound structures (B and C).

Figure S4. The angle distributions of Gln9 in chain A when forming H-bonds with DNA. (A) The angle is mainly at 180° when there is no H-bond formed. (B-D) The angle is mainly at -60° when multiple H-bonds are formed.

Figure S5. The potential energy between Arc repressor and DNA during simulation. During most of the simulation time, wild-type complex structure has lower potential energy than the mutant F10V, suggesting the wild-type is more stable. (A) Coulomb potential and (B) L-J potential.