A coarse-grain three-site-per-nucleotide model for DNA with explicit ions

Abstract

The "three sites per nucleotide" (3SPN) model provides a coarse-grained representation of nucleic acids for simulation of molecular processes. Previously, this model has relied on an implicit representation of the surrounding ionic environment at the level of Debye-Hückel theory. In this work, we eliminate this limitation and present an explicit representation of ions, both monovalent and divalent. The coarse-grain ion-ion and ion-phosphate potential energy functions are inferred from all-atom simulations and parameterized to reproduce key features of the local structure and organization of ions in bulk water and in the presence of DNA. The resulting model, 3SPN.1-I, is capable of reproducing the local structure observed in detailed atomistic simulations, as well as the experimental melting temperature of DNA for a range of DNA oligonucleotide lengths, CG-content, Na + concentration, and Mg 2 + concentration.

Inferring bulk self-assembly properties from simulations of small systems with multiple constituent species and small systems in the grand canonical ensemble

“…Nonetheless, if comparisons of models with bulk experiment are to be made, then it is sensible to apply these corrections, as failure to do so is analogous to reporting results obtained with a faulty algorithm that causes a quantitative error. Although mesoscale models are never going to give precise descriptions of all the properties of a system, many have recently been used to provide quantitative comparisons of yields with experiment, [46][47][48][50][51][52][54][55][56][57][58]61 and hence should consider the corrections presented here. Other authors have not compared to experiment, but have related equilibrium thermodynamics obtained from single-target simulations to bulk simulations of the same model.…”

“…Multi-species assembly A number of authors have taken cluster yields in canonical simulations of single-target assembly as directly applicable to bulk systems. 35,39,[50][51][52]54 These examples involve dimers and clusters of a single species, which we analysed in our earlier work. 63 Interesting structures, however, are not exclusively dimers or formed from identical subunits.…”

“…Many of the mesoscopic models discussed in Section I treat the solvent implicitly. [18][19][20][21]30,32,[35][36][37][38][39][40][41][45][46][47][48][50][51][52][53][54][55][56][57][58][59] With the solvent treated implicitly, model clusters (at low enough concentrations) will behave ideally except for when they bind to form a larger cluster. A self-consistent methodology for comparing these models to experiment would be to assume that clustering causes no change to the pressure of the system: i.e., the partial pressure of solute is negligible and that the change of the solvent/solute interaction due to clustering has no effect on pressure.…”

“…[22][23][24][25]35,36,39,[46][47][48][50][51][52][53][54][55][56][57][58]61,62 One obvious drawback of this approach is that any interactions between clusters (or tendencies to aggregate into macroscopic objects) are not observed. In many cases, however, monomers are in dilute solution and interactions between correctly formed targets are largely short-ranged and repulsive, and so these effects may be negligible.…”

“…43 Additionally, reflecting the growth of DNA nanotechnology, 44 many coarse-grained models of DNA assembly have recently been proposed. [45][46][47][48][49][50][51][52][53][54][55][56][57][58][59] In many cases, these simulations report quantitative measures of assembly, such as the fraction of particles involved in clusters of a certain size. Experiments and thermodynamic theories typically involve bulk systems with a large number of particles, capable of forming many target structures.…”