His also offers a versatile target for substitution with analogs like L-Ala(4'-pyridyl) (Pyr) or L-Ala(4-thiazolyl) (Tha) to modify its ring size and electronic properties. Asn can be substituted for Cit to lengthen its side chain. Finally, potential Ala sites can be replaced by α-aminoisobutyric acid (Aib) to induce the helicity of the DNA binding domain. In addition to the non-proteogenic amino acids, we also included natural residues (e.g., His to Tyr, Asn to Gln, and Lys to Arg), which can result from genetic mutations, to assess the impact of these changes on the TF-DNA interactions.