Dynamics of a double stranded DNA oligomer: Mode-coupling diffusion approach and reduced rigid fragment models

The local dynamics of a double stranded DNA fragment [d(CpGpCpApApApTpTpTpG pCpG)](2) of twelve base pairs is;obtained to second order in the mode-coup ling expansion of the Smoluchowski diffusion theory. The DNA is considered a fluctuating three-dimensional (3D) structure underg oing rotational diffusion. The starting structure for the calculations is t he B canonical structure of the fragment, while the fluctuations are evalua ted using molecular dynamics simulations, with the ensemble averages approx imated by time averages along a trajectory of length 1.5 ns. The rotational dynamics of the bonds along the double strands are calculated and compared to experimental NMR relaxation rates of different C-13 along the sequence: R( C-z), R(C-xy) and R(H-z --> C-z). For a fluctuating 3D structure the mo de-coupling diffusion theory is found to be in good agreement with several relative characteristics of the experimental relaxation parameters, while m otivations are given for the few differences which are due mainly to poor s tatistics or to inaccuracies in the diffusion model. With a view to applica tion to larger DNA fragments, discussion is dedicated to the validity of re ducing the number of degrees of freedom in the double helix statistics by g rouping the atoms in rigid fragments (e.g. the backbone atoms, the sugar at oms and the base atoms of each nucleotide). Consideration is given to the e ffect on local dynamics properties of reduced descriptions that include onl y three or four rigid bodies per nucleotide as well as five rigid bodies pe r base pair. It is found that in general these approximations almost unifor mly produce slight increase in the correlation time pattern, which grows as the rigidity in the model increases. The relative effects on the dynamic p attern for the most accurate rigid body models are modest. The errors in C1 ' and C5' mobilities are more significant if C5' is included in the backbon e rigid body. These results offer new tools to analyse NMR relaxation behaviour and new p erspectives in studying the role of dynamics in biological macromolecules.