Ion motions in molecular dynamics simulations on DNA

Abstract

Counterions play a significant role in DNA structure and function, and molecular dynamics (MD) simulations offer the prospect of detailed description of the dynamical structure of ions at the molecular level. However, the motions of mobile counterions are notably slow to converge in MD on DNA. Obtaining accurate and reliable MD simulations requires knowing just how much sampling is required for convergence of each of the properties of interest. To address this issue, MD on a d(CGCGAATTCGCG) duplex in a dilute aqueous solution of water and 22 Na ؉ counterions was performed until convergence was achieved. The calculated first shell ion occupancies and DNA-Na ؉ radial distribution functions were computed as a function of time to assess convergence, and compared with relaxation times of the DNA internal parameters shift, slide, rise, tilt, roll, and twist. The sequence dependence of fractional occupancies of ions in the major and minor grooves of the DNA is examined, and the possibility of correlation between ion proximity and DNA minor groove widths is investigated. C ounterion structures and motions have been implicated in recent ideas about sequence effects on DNA structure axis curvature and ligand-induced bending (1-7). In each of these theories, the local interactions of ions with polyionic DNA complement the effects described by counterion condensation (CC) theory (8) and the Poisson Boltzmann (PB) equation (9,10). Although the effect of ions and ionic strength on DNA structural and thermodynamics properties are implied from diverse experiments, obtaining a fully detailed molecular model of the ions interacting with DNA based on these results is usually not possible. Oligonucleotide crystal structures reveal only the few ions that are ordered and can be unequivocally assigned. The positions of ions around DNA are generally underdetermined in experiments based on biophysical methods. Recent studies requiring this information have turned to large-scale molecular dynamics (MD) simulations to obtain computational models (11). However, in MD modeling, the complex aggregate of oligonucleotide, water, counterions, and coions is slow to fully stabilize, and ion motions are a rate-determining step in total convergence (12). Current reviews of MD on DNA (12)(13)(14) indicate that all simulations to date are based on considerably shorter trajectories. Therefore, we initiated a project aimed at obtaining demonstrably converged results on ion structures and motions. A related question is the sensitivity of the fast internal motions of the DNA to ion convergence. Our analysis is based on an MD simulation on the prototype B-form duplex d(CGC-GAATTCGCG) in a dilute aqueous solution of water and Na ϩ counterions carried out on a supercomputer until the point of convergence could be reliably determined. The trajectories are used to study the sequence dependence of ion distributions, the DNA-Na ϩ radial distribution functions, and the sensitivity of groove widths to ion proximity. The simulations are used as a basis for a compa...

X-ray diffraction “fingerprinting” of DNA structure in solution for quantitative evaluation of molecular dynamics simulation

“…8 and 9), suggesting that simulated DNA structure reached equilibration by 1 ns. Similar findings were previously noted in simulations carried out to 60 ns, although counterion distributions were found not to have equilibrated (27). These observations and the present data suggest a possibility that final DNA structure equilibration might be linked to long-range counterion redistribution.…”

Role and Applications of Electrostatic Effects on Nucleic Acid Conformational Transitions and Binding Processes

“…They reported that the "cloud" of counterions around the DNA under no added salt conditions is consistent with Manning's counterion condensation theory, with 76% of the ions condensed around the DNA (Young et al, 1997). A more recent MD simulation on a comparable system (DDD, 22 Na + ions, ≈4000 waters, 60 ns simulation) found similar results (Ponomarev et al, 2004). More recently, the net neutralization of DNA charge by core histones and surrounding counterions in the presence of ≈ 50,000 water molecules was considered after a 200 ns MD simulation (Materese et al, 2009).…”

Effect of Ionic Ordering in Conductivity Experiments of DNA Aqueous Solutions

“…The results have been showed that the dynamics of counterions in close vicinity to DNA surface is modulated by the charged atomic groups of the double helix backbone. Part of the time counterions spend in complex with DNA (about 1 ns) and another part in free state [28][29][30][31]. Free counterions determine the conductivity of DNA solution in many respects that has been taken into consideration in phenomenological models [24,26].…”