Non-equilibrium all-atom molecular dynamics simulations of free and tethered DNA molecules in nanochannel shear flows

In order to gain insight into the mechanical and dynamical behaviour of free and tethered short chains of ss/ds DNA molecules in flow, and in parallel to investigate the properties of long chain molecules in flow fields, we have developed a series of quantum and molecular methods to extend the well developed equilibrium software CHARMM to handle non-equilibrium dynamics. These methods have been applied to cases of DNA molecules in shear flows in nanochannels. Biomolecules, both free and wall-tethered, have been simulated in the all-atom style in solvent-filled nanochannels. The new methods were demonstrated by carrying out NEMD simulations of free single-stranded DNA (ssDNA) molecules of 21 bases as well as double-stranded DNA (dsDNA) molecules of 21 base pairs tethered on gold surfaces in an ionic water shear flow. The tethering of the linker molecule (6-mercapto-1-hexanol) to perfect Au(111) surfaces was parametrized based on density functional theory (DFT) calculations. Force field parameters were incorporated into the CHARMM database. Gold surfaces are simulated in a Lennard-Jones style model that was fitted to the Morse potential model of bulk gold. The bonding force of attachment of the DNA molecules to the gold substrate linker molecule was computed to be up to a few nN when the DNA molecules are fully stretched at high shear rates. For the first time, we calculated the relaxation time of DNA molecules in picoseconds (ps) and the hydrodynamic force up to a few nanoNewtons (nN) per base pair in a nanochannel flow. The velocity profiles in the solvent due to the presence of the tethered DNA molecules were found to be nonlinear only at high shear flow rates. Free ssDNA molecules in a shear flow were observed to behave differently from each other depending upon their initial orientation in the flow field. Both free and tethered DNA molecules are clearly observed to be stretching, rotating and relaxing. Methods developed in this initial work can be incorporated into multiscale simulations including quantum mechanical, molecular and the microfluidic continuum regimes. The results may also be useful in extending existing macroscopic empirical models of DNA response dynamics in shear flows.