Close encounters with DNA

Abstract

Over the past ten years, the all-atom molecular dynamics method has grown in the scale of both systems and processes amenable to it and in its ability to make quantitative predictions about the behavior of experimental systems. The field of computational DNA research is no exception, witnessing a dramatic increase in the size of systems simulated with atomic resolution, the duration of individual simulations and the realism of the simulation outcomes. In this topical review, we describe the hallmark physical properties of DNA from the perspective of all-atom simulations. We demonstrate the amazing ability of such simulations to reveal the microscopic physical origins of experimentally observed phenomena and we review the frustrating limitations associated with imperfections of present atomic force fields and inadequate sampling. The review is focused on the following four physical properties of DNA: effective electric charge, response to an external mechanical force, interaction with other DNA molecules and behavior in an external electric field.

Introducing improved structural properties and salt dependence into a coarse-grained model of DNA

“…Classical all-atom approaches, where every atom of DNA and the surrounding solvent is modelled as a point particle with effective interactions, have been widely employed to study small DNA motifs 14,15 and have recently been applied to larger DNA systems. [16][17][18] However, simulating rare-event processes such as the breaking or formation of base pairs remains a challenge with these models, with µs time scales being the limit of what is currently accessible. 18 At the other end of the scale, theoretical approaches have been developed to understand certain large-scale properties of DNA.…”

Understanding the origin of liquid crystal ordering of ultrashort double-stranded DNA

“…Whereas, we find that even in the SH configuration, which corresponds to low stacking area, we obtain a value of 6 kcal/mol for the free energy of binding. The higher values seem to stem from the nature of the force fields, which have a tendency of overestimating the stacking free energies [48,49]. This overestimation will lead to columns that are rigid and would stabilize the nematic phase at higher temperatures.…”

Multiscale simulation of DNA

“…No matter the approach used to derive the force-field, nor the final application of the model, one of the key difficulties specific to the DNA coarse graining is the correct handling of long-range electrostatics, something that is crucial to correctly represent one of the most highly charged naturally occurring polyelectrolytes [151]. Only a few models incorporate electrostatic explicitly [127,128,130,141•] assigning partial charges to the DNA beads, but in all the cases the environment around DNA has been taken into account at some degree, by using implicit or explicit approaches.…”