Computational docking simulations of a DNA-aptamer for argininamide and related ligands

The binding properties of sequence-specific nucleic acids (aptamers) to low-molecular-weight ligands, macromolecules and even cells attract substantial scientific interest. These ligand-DNA complexes found different applications for sensing, nanomedicine, and DNA nanotechnology. Structural information on the aptamer-ligand complexes is, however, scarce, even though it would openup the possibilities to design novel features in the complexes. In the present study we apply molecular docking simulations to probe the features of an experimentally documented L-argininamide aptamer complex. The docking simulations were performed using AutoDock 4.0 and YASARA Structure software, a well-suited program for following intermolecular interactions and structures of biomolecules, including DNA. We explored the binding features of a DNA aptamer to L-argininamide and to a series of arginine derivatives or arginine-like ligands. We find that the best docking results are obtained after an energy-minimization of the parent ligand-aptamer complexes. The calculated binding energies of all mono-substituted guanidine-containing ligands show a good correlation with the experimentally determined binding constants. The results provide valuable guidelines for the application of docking simulations for the prediction of aptamer-ligand structures, and for the design of novel features of ligandaptamer complexes.