Open-Boundary Molecular Dynamics of a DNA Molecule in a Hybrid Explicit/Implicit Salt Solution

Abstract

The composition and electrolyte concentration of the aqueous bathing environment have important consequences for many biological processes and can profoundly affect the behavior of biomolecules. Nevertheless, because of computational limitations, many molecular simulations of biophysical systems can be performed only at specific ionic conditions: either at nominally zero salt concentration, i.e., including only counterions enforcing the system's electroneutrality, or at excessive salt concentrations. Here, we introduce an efficient molecular dynamics simulation approach for an atomistic DNA molecule at realistic physiological ionic conditions. The simulations are performed by employing the open-boundary molecular dynamics method that allows for simulation of open systems that can exchange mass and linear momentum with the environment. In our open-boundary molecular dynamics approach, the computational burden is drastically alleviated by embedding the DNA molecule in a mixed explicit/implicit salt-bathing solution. In the explicit domain, the water molecules and ions are both overtly present in the system, whereas in the implicit water domain, only the ions are explicitly present and the water is described as a continuous dielectric medium. Water molecules are inserted and deleted into/from the system in the intermediate buffer domain that acts as a water reservoir to the explicit domain, with both water molecules and ions free to enter or leave the explicit domain. Our approach is general and allows for efficient molecular simulations of biomolecules solvated in bathing salt solutions at any ionic strength condition.

Density–Nematic Coupling in Isotropic Linear Polymers: Acoustic and Osmotic Birefringence

“…It is challenging to determine the macroscopic parameters of real polymeric systems by conducting microscopic simulations with known force fields, and fitting the extracted fluctuation amplitudes with theoretical expressions as we have done for our model system. In this respect, DNA is of particular interest: a recently developed open‐boundary molecular dynamics of a DNA molecule in explicit salt–hybrid explicit/implicit water solution would enable DNA simulations at lower, physiological salt concentrations . At this stage, let us make an estimate of the coupling strength for DNA, making use of the theoretical prediction in Equation .…”

From System Modeling to System Analysis: The Impact of Resolution Level and Resolution Distribution in the Computer-Aided Investigation of Biomolecules

“…Several examples exist of simulation schemes including atomistic and continuum descriptions for the simulations of water ( Brünger et al, 1984 ; Beglov and Roux, 1994 ; Im et al, 2001 ; Lee et al, 2004 ; Deng and Roux, 2008 ; Wagoner and Pande, 2011 ; Wagoner and Pande, 2013 ; Petsev et al, 2015 ). Attempts of triple-scale simulation of liquid water have also been performed, by concurrently coupling atomistic, CG, and continuum models ( Delgado-Buscalioni et al, 2009 ; Zavadlav et al, 2018 ). Applications of an atomistic/continuum representation of the solvent for biomolecular studies have been performed in Wagoner and Pande (2018) , where the boundary between the explicit/continuum solvent models can adapt itself in response to the conformational fluctuations of the atomistic peptide simulated; and in Hu et al (2019) , for a multi-resolution simulation of protein diffusion in water under a steady shear flow.…”

Particle–Continuum Coupling and its Scaling Regimes: Theory and Applications

“…[ 68 ] The computational burden is drastically alleviated by implicit solvent models but if one is interested in hydrodynamic interactions the inclusion of explicit solvent is in many cases unavoidable. [ 69,70 ]…”

“…Another example of combining AdResS with a mass, momentum, and energy reservoir and imposing a local pressure tensor and a heat flux across the boundaries, [ 185 ] thus enabling Grand Canonical MD simulations, is provided by Open Boundary Molecular Dynamics (OBMD) method. [ 6,70,115–117 ]…”