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

Abstract

In order to gain insight into the mechanical and dynamical behaviour of free and tetheredshort chains of ss/ds DNA molecules in flow, and in parallel to investigate the properties oflong chain molecules in flow fields, we have developed a series of quantum andmolecular methods to extend the well developed equilibrium software CHARMM tohandle non-equilibrium dynamics. These methods have been applied to casesof DNA molecules in shear flows in nanochannels. Biomolecules, both free andwall-tethered, have been simulated in the all-atom style in solvent-filled nanochannels.The new methods were demonstrated by carrying out NEMD simulations of freesingle-stranded DNA (ssDNA) molecules of 21 bases as well as double-strandedDNA (dsDNA) molecules of 21 base pairs tethered on gold surfaces in an ionicwater shear flow. The tethering of the linker molecule (6-mercapto-1-hexanol) toperfect Au(111) surfaces was parametrized based on density functional theory(DFT) calculations. Force field parameters were incorporated into the CHARMMdatabase. Gold surfaces are simulated in a Lennard-Jones style model that wasfitted to the Morse potential model of bulk gold. The bonding force of attachmentof the DNA molecules to the gold substrate linker molecule was computed tobe up to a few nN when the DNA molecules are fully stretched at high shearrates. For the first time, we calculated the relaxation time of DNA molecules inpicoseconds (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 tothe presence of the tethered DNA molecules were found to be nonlinear only athigh shear flow rates. Free ssDNA molecules in a shear flow were observed tobehave differently from each other depending upon their initial orientation inthe flow field. Both free and tethered DNA molecules are clearly observed to bestretching, rotating and relaxing. Methods developed in this initial work can beincorporated into multiscale simulations including quantum mechanical, molecular andthe microfluidic continuum regimes. The results may also be useful in extendingexisting macroscopic empirical models of DNA response dynamics in shear flows.