(253ar) Hybridization in DNA Self-Assembled Monolayer Studied with Atomistic Simulation and Free Energy Computation

The implantation of short nucleic acid fragments, ranging between 16-27 nucleic acids in length, on self-assemble surface has been shown to be a new class of novel diagnostic markers for diseases such as cancer. The sensitivity of such biochips is highly dependent on total hybridized amount of target strands from the bulk into the self-assembled monolayer (SAMs) of complementary strands grafted onto the substrate surface. Various factors affect the hybridization processes, such as surface morphology, surface coverage density, ion strength and target DNA concentration. To study the effects of those factors, we performed molecular dynamics simulations and free energy computation to study the morphology of DNA brush grafted onto a cristobalite substrate surface as well as its hybridization efficiency. Different DNA SAMs morphologies as a function of surface coverage density and the corresponding hybridized efficiency were examined. For the particular sequence we studied, an unhybridized DNA strand exhibits flexible coil, whereas a hybridized double strand displays a rigid rod structure. Counter ions in the system were attracted to the nucleic acid strands due to negative charged DNA chains. Moreover, lower diffusive activities of ions were observed inside condensed DNA SAMs. Hybridization free energy of DNA SAMs was predicted. Our research will facilitate the development of new biodevices based on nucleic acid hybridization.