A Simple Solvation Model Along with A Multibody Dynamics Strategy (MBO(N)D) Produces Stable DNA Simulations that are Faster than Traditional Atomistic Methods

Abstract

We are developing solvation strategies that complement the speed advantage of MBO(N)D (a multibody simulation approach developed by Moldyn) for simulating biomolecular systems. In this report we propose to approximate the effect of bulk waters on DNA by using only a thin layer of waters proximate to the surface of DNA (which we will call the ‘thin shell approach’ or TSA). We will show that the TSA combined with substructuring (the grouping of atoms into rigid or flexible bodies) of the Dickerson dodecamer produces good comparisons with standard atomistic methods (over a nanosecond trajectory) as judged by a variety of DNA specific geometric (e.g., CURVES output) and dynamics (power spectra) properties. The MBO(N)D method, however, was faster than atomistic by a factor of six using the same solvation strategy and factor of 70 when compared to fully solvated atomistic system. The key to the speed of MBO(N)D is in its ability to use large time steps during dynamics. By keeping only a shell of molecules of water proximate to the dodecamer, we limit artifacts due to surface tension at the water-vacuum interface. These proximate waters are fairly immobile as compared to those in bulk and therefore do not severely limit the time step in the simulation. The strengths and limitations of this solvation approach, and future directions, will also be discussed.