Molecular-dynamics simulations of insertion of chemically modified DNA nanostructures into a water-chloroform interface.

DNA-based two-dimensional and three-dimensional arrays have been used as templates for the synthesis of functional polymers and proteins. Hydrophobic or amphiphilic DNA arrays would be useful for the synthesis of hydrophobic molecules. The objective of this study was to design a modified amphiphilic double crossover DNA molecule that would insert into a water-chloroform interface, thus showing an amphiphilic character. Since experiments for such designs are tedious, we used molecular-dynamics simulations to identify and optimize the functional groups to modify the DNA backbone that would enable insertion into the water-chloroform interface before synthesis. By methylating the phosphates of the backbone to make phosphonates, in combination with placing a benzyl group at the 2' position of the deoxyribose rings in the backbone, we observed that the simple B-DNA structure was able to insert into the water-chloroform interface. We find that the transfer free energy of methylated benzylated DNA is better than that of either just methylated or benzylated DNA. The driving force for this insertion comes from the entropic contribution to the free energy and the favorable van der Waals interaction of the chloroform molecules with the methyl and benzyl groups of the DNA.