Role of Gln50

The homeodomains of the Antennapedia type bind to the DNA sequence XXATTA, and, as the previous section indicates, Gln50 and Met54 are the two residues that contact the two variable base pairs.

A biochemical study on the fushi-tarazu homeodomain, which is closely related to Antennapedia, showed that a mutation of Gln at this postion to Lys resulted in greatly decreased affinity to the original DNA sequence CCATTA ($\alpha$-strand). A compensating mutation of the DNA to GGATTA restored the binding affinity and even surpassed the original [2,7]. Similar biochemical studies were performed with the engrailed homeodomain, in which mutation Gln to Lys at position 50 required a change in the DNA from TAATTA to GGATTA [8], and the crystal structure of the mutant complex was determined [9].

These results point to residue 50 as the key position in recognizing various sequences of type XXATTA.

The goal of this study was to simulate the mutation Gln50 to Lys in the Antennapedia homeodomain and a corresponding mutation CC to GG in the DNA at positions 6 and 7, and to follow the intermolecular contact network during molecular dynamics simulations. Our results conform with the predictions of the above study on the fushi-tarazu homeodomain-DNA complex.