Certain small polyamide molecules, analogs of distamycin, are known to bind in a 2:1 motif in the minor groove of DNA with strong binding affinity and sequence specificity depending on the structure of the small molecule.  Until now, docking studies have focused on accurately binding ligand-substrate complexes in a 1:1 motif.  However, the need exists for accurate development of multi-ligand docking techniques.  In this study, commercially available software packages (GOLD, Autodock) were used to dock a polyamide, f-IPI, into the minor groove of the 10-mer DNA sequence CCACGCGTGG, and compared to 1)   X-ray structures of a similar complex, 2) manual docking studies that were guided by NOE contacts performed in our group, and 3) snapshots from MD simulations of the manually docked complex.

Multi-ligand docking in the minor groove of DNA

245th National Meeting (2013)

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