It is generally taken for granted that water is essential for life and thus called the 'lubricant of life'. Understanding the dynamics of water molecules at the surfaces of self-organized assemblies and complex biological macromolecules in aqueous solution has been a subject of intense research for a long time. In order to emphasize the difference between water molecules at the surface of biomolecules and self-assemblies (known as biological water) and those in the bulk, one often represents the former as a hydration layer which is assumed to be a distinct entity. The characteristic features of water molecules in the hydration layer, where the hydrogen bond network gets locally disrupted, differ significantly from those of bulk, and thus pose another set of interesting dynamical problems. This is an important issue because water molecules are found in abundance at the interfaces of biomolecules (proteins, DNA etc.) and self-assemblies (e.g. micelles), and they control the structure, function, and reactivity of many natural and biological systems. A complete understanding of these aqueous solutions crucially not only depends on their time-averaged structure but also on the dynamical properties of the hydration layer.
We employ atomistic molecular dynamics (MD) simulations to understand varying water dynamics at the minor and major grooves of a 38 base-pair long DNA duplex in water. In order to understand and quantify the diversity in the nature of hydrogen bond due to many hydrogen bond donors and acceptors present in the four bases, we have undertaken study of hydrogen bond lifetime correlation functions (HBLTCF) of all the specific hydrogen bonds between the base atoms and water molecules. We find that the HBLTCF are in general multi-exponential, with the average lifetime depending significantly on the specificity and may thus be biologically relevant. The average hydrogen bond life time is longer in the minor groove than that in the major groove by almost a factor of two. Analysis further shows that water hydrogen bonds with phosphate oxygen have substantially shorter lifetimes than those with the groove atoms.
The decay of the average hydrogen bond life time correlation functions (HBLTCF) for the hydrogen bond between base and water molecule present at the minor and the major grooves of DNA. For comparison, we show the same function for a pair of water molecules in the bulk.
We have also computed the energy-energy time correlation function (TCF) of the four individual bases (A, T, G and C) to characterize the solvation dynamics. All the TCFs display highly non-exponential decay with time. The TCF of each base shows initial ultra-fast decay (~60-80 fs) followed by two intermediate components (~1 ps, and ~20-30 ps), in near complete agreement with a recent time domain experiment on DNA solvation. Interestingly, the solvation dynamics of each of the four different nucleotide bases exhibits rather similar time scales.
Plot of the time dependence of the total solvation energy time correlation function (TCF) for the all the different bases
Through an analysis of partial
solvation TCFs , we
find that the slow decay originates mainly from the interaction of the
nucleotides with the dipolar water molecules and the counterions. An
interesting negative cross-correlation between water and counterions is
observed which makes an important contribution to relaxation at
intermediate to longer times.
(top) Decay of the partial solvation time correlation functions (direct and cross) for a base of type G to identify the contributions different interactions
(bottom) The time dependent fluctuation in the energy contribution from ions and water molecules as a function of time along an MD trajectory for a G base showing the negative cross-correlation between the water and ionic contributions over a segment of trajectory.
Understanding of dynamic and thermodynamic properties of the hydration layer is important to understand the role of water molecule in several biological processes. Recently, we have calculated those properties of the hydration layer of the major and minor groove of a B-DNA using extensive computer simulation followed by the use of Two Phase Thermodynamic model (commonly referred as 2PT model). We have calculated velocity time correlation function (VCF) of the water molecule in the major and minor groove separately and compared that with the bulk water. We have huge difference in the VCF between the groove water and bulk water indicating the differences in the dynamical properties between them. In fact, we have found that the groove water molecules, especially minor groove, are dynamically more constrained than bulk.
We have calculated the entropy of water molecules of different regions of the aqueous DNA and found that groove water, especially minor groove, molecules have lower entropy than that of bulk water. Difference of the entropy of the groove water and bulk water are comparable to the entropy change due to melting of ice which again supports the ice-like structure of the hydration layer. See the following table (click to enlarge) for the numerical values of different quantities calculated for different region of water molecules.