Molecular Modeling and Simulations of DNA at Graphene-Water Interfaces towards Developing Biosensors and Drug Delivery Vehicles

Abstract

The biocompatibility of Graphene oxide (GO) surfaces and their preferential affinity to single stranded DNA (ssDNA) over double stranded DNA (dsDNA) make GO-ssDNA complexes an attractive target for drug delivery applications. GO-ssDNA complexes also hold promise as biosensors: fluorescence can be achieved by desorption of fluorescently tagged ssDNA from GO surfaces by their complementary strands or DNA-binding proteins in solution. To tune nucleic acid sequences for targeting specific molecules, and to achieve high sensing abilities, it is important to quantify the interaction of individual nucleobases (A, T, G & C) and small oligonucleotides with GO or graphene surfaces, and understand the molecular mechanisms involved. Although experimental studies in the past (ITC, AFM) have focused on graphene-nucleobase interaction in water, and a few theoretical studies have focused on the same interaction in vacuum, a quantitative understanding of graphene-nucleic acid interaction still remains elusive. To this end, we performed molecular dynamics simulations, guided by dispersion-corrected density functional theory (DFT) and ITC experiments, to accurately quantify and understand the molecular mechanism of nucleobases and nucleosides binding to graphene surfaces in water. As part of this work, we modified the AMBER-99 all-atom molecular dynamics force-field parameters to accurately capture the van der Waals interaction between the atoms of the nucleobases and graphene. We rescaled the size of the graphene carbon and nucleobase atoms to match the graphene-nucleobase interaction energy profile in vacuum obtained using DFT calculations, and further rescaled the interaction energies to reproduce the binding free-energies in water obtained through ITC experiments. Our results provide a quantitative understanding of nucleobase-graphene interactions, and also build a platform to understand ssDNA binding to graphene surfaces, duplex formation at the graphene-water interface and their subsequent release to the bulk.