BROMOC-D: Brownian Dynamics/Monte-Carlo Program Suite to Study Ion and DNA Permeation in Nanopores

Abstract

A theoretical framework is presented to model ion and DNA translocation across a nanopore confinement under an applied electric field. A combined Grand Canonical Monte Carlo Brownian Dynamics (GCMC/BD) algorithm offers a general approach to study ion permeation through wide molecular pores with a direct account of ion–ion and ion–DNA correlations. This work extends previously developed theory by incorporating the recently developed coarse-grain polymer model of DNA by de Pablo and colleagues [Knotts, T. A.; Rathore, N.; Schwartz, D. C.; de Pablo, J. J. J. Chem. Phys. 2007, 126] with explicit ions for simulations of polymer dynamics. Atomistic MD simulations were used to guide model developments. The power of the developed scheme is illustrated with studies of single-stranded DNA (ss-DNA) oligomer translocation in two model cases: a cylindrical pore with a varying radius and a well-studied experimental system, the staphylococcal α-hemolysin channel. The developed model shows good agreement with experimental data for model studies of two homopolymers: ss-poly(dA)n and ss-poly(dC)n. The developed protocol allows for direct evaluation of different factors (charge distribution and pore shape and size) controlling DNA translocation in a variety of nanopores.

A Coarse-Grained Model of Unstructured Single-Stranded DNA Derived from Atomistic Simulation and Single-Molecule Experiment

“…23,24,26−28,32−36,38 Validation of the single-stranded properties produced by DNA models against experimental observables has been sparse. Because RNA structures typically contain a significant amount of single-stranded material, we may expect that CG models of RNA 25,37 may better represent single-stranded nucleic acid conformations.…”

Dynamic Monte Carlo Simulation of Coupled Transport through a Narrow Multiply-Occupied Pore

“…Simulations of these effects would be interesting (using one of the electrostatic algorithms of Refs. [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][44][45][46][47] and can be the topic of future studies. However, the main conclusions of this study would not change.…”

The power of coarse graining in biomolecular simulations

“…The authors measured roughly three orders of magnitude speedup as compared with atomistic simulations for short dsDNAs. The model has been refined (3SPN.1)123 to describe DNA hybridization and to model ions explicitly 124–126. Very recently, the 3SPN.2127 model that does not use Gō-potentials for stacking was introduced.…”