Glass transition in DNA from molecular dynamics simulations.

Abstract

Molecular dynamics simulations of the oligonucleotide duplex d(CGCGCG)2 in aqueous solution are used to investigate the glass transition phenomenon. The simulations were performed at temperatures in the 20 K to 340 K range. The mean square atomic fluctuations showed that the behavior of the oligonucleotide duplex was harmonic at low temperatures. A glass transition temperature at 223 K to 234 K was inferred for the oligonucleotide duplex, which is in agreement with experimental observations. The largest number of hydrogen bonds between the polar atoms of the oligonucleotide duplex and the water molecules was obtained at the glass transition temperature. With increasing temperature we observed a decrease in the average lifetime of the hydrogen bonds to water molecules.Dynamical aspects of nucleic acids are of great interest as a means to increase the understanding of the DNA double helix. Nuclear magnetic resonance experiments and molecular dynamics (MD) simulations have been used to gain insight into the internal motion of oligonucleotide duplexes (1, 2).The glass transition phenomenon, which has recently been reviewed (3), has so far mainly been examined for proteins using neutron scattering experiments (4, 5), x-ray diffraction (6), Mossbauer (7) and MD simulations (8-11). In pure water, the number of different hydrogen bonds was observed to increase with increasing temperature (8). In MD studies of myoglobin, the glass transition was in part due to torsional jumping (9), and a significant increase was found in the anharmonic component of atomic positional fluctuations above the glass transition temperature upon hydration (10). Protein dynamics from MD simulations at low temperatures was observed to depend on the way the low temperature state is achieved (11). A previous experiment (12) indicated that the glass transition of a protein was induced by the surrounding solvent. Indications of a glass transition in solid calf thymus DNA, with around 40% water content, have been given by thermally stimulated depolarization current measurements (13,14). The origin of the glass transition was interpreted as the melting of hydrogen bonds of bound water molecules on the surface of the DNA (13). At low temperatures part of the bound water, especially in the first hydration shell, of DNA was in the glass form (14). From dielectric relaxation spectroscopy on solid calf thymus DNA at water content up to 32% the glass transition was estimated to 238 K (15).We present MD simulations of the oligonucleotide duplex d(CGCGCG)2 in aqueous solution. Simulations were performed at 12 different temperatures between 20 K and 340 K. The mean square atomic fluctuations were partitioned into contributions from the different constituents, bases, sugar riboses, and phosphate groups of DNA. The influence of solvent was examined by calculating the hydrogen bonds between the polar atoms of the oligonucleotide duplex and the water molecules. The analysis of the MD simulations permits us to interpret the dynamical phenomenon that underli...

Temperature dependence of fast fluctuations in single- and double-stranded DNA molecules: a neutron scattering investigation

“…Such dynamics, which becomes more evident with increasing temperature, is consistent with methyl group reorientation, as previously discussed. Then a second anharmonic onset, the so-called dynamical transition, observed only in the hydrated samples, occurs at the estimated temperature T d = 230 -240 K. This value turns out to be in agreement with previous theoretical [26] and experimental [19,20,27] results. MD simulations on hexamer oligonucleotide duplex in aqueous solution localised a glass-like dynamical transition in the 223 -234 K range [26].…”

“…Then a second anharmonic onset, the so-called dynamical transition, observed only in the hydrated samples, occurs at the estimated temperature T d = 230 -240 K. This value turns out to be in agreement with previous theoretical [26] and experimental [19,20,27] results. MD simulations on hexamer oligonucleotide duplex in aqueous solution localised a glass-like dynamical transition in the 223 -234 K range [26]. From dielectric relaxation spectroscopy on hydrated solid calf thymus DNA the transition was found to take place at around 238 K [27], while through a quasielastic neutron scattering study on Li-DNA fibres Sokolov and co-workers [19,20] found the rise of a strong anharmonicity above 210 K for samples hydrated at 11% or more.…”

The puzzling unsolved mysteries of liquid water: Some recent progress

“…Next we explore the hypothesis [50] that the observed glass transition in biomolecules [12,[51][52][53][54][55][56][57][58][59][60][61][62][63]71] is related to the liquid-liquid phase transition using MD simulations. Specifically, Kumar et al [50] studied the dynamic and thermodynamic behavior of lysozyme and DNA in hydration TIP5P water, by means of the software package GROMACS [64] for: (i) an orthorhombic form of hen egg-white lysozyme [65] and (ii) a Dickerson dodecamer DNA [66] at constant pressure P ¼ 1 atm, several constant temperatures T, and constant number of water molecules N (NPT ensemble).…”

Glass Transition in Biomolecules and the Liquid-Liquid Critical Point of Water

“…Previous simulations [10] and experiments [9] suggest a "glass-like" transition of DNA around temperature 230 K. Hence to test if the dynamic crossover depends on the solute, we performed a parallel study of the DNA Dickerson dodecamer [24]. We find that fluctua- Note Added in Proof: After this work was submitted, we learned of interesting parallel work on silicon, which also interprets structural change in g(r) and S(q) as crossing the Widom line [35].…”

“…An important issue is to determine the effects of hydration water on this dynamical transition [6,7,8,9,10].…”