Mode-coupling smoluchowski dynamics of a double-stranded DNA oligomer

Area of Science:

• Computational Chemistry
• Biophysics
• Molecular Dynamics

Background:

• Understanding the local dynamics of double-stranded DNA is crucial for comprehending its function.
• Previous models often simplified DNA's complex three-dimensional fluctuating structure.

Purpose of the Study:

• To calculate the local dynamics of a specific DNA sequence, d(TpCpGpCpG)(2).
• To compare calculated (13)C-NMR spin-lattice relaxation times (T(1)) with experimental data.
• To assess the applicability of mode-coupling theory and molecular dynamics simulations for studying complex biological structures.

Main Methods:

• Applied second-order mode-coupling expansion of Smoluchowski diffusion theory.
• Derived time correlation functions for bond variables.
• Utilized molecular dynamics simulations (1 ns trajectory) to evaluate fluctuations.
• Calculated (13)C-NMR spin-lattice relaxation times (T(1)) for various atoms along the DNA chain.

Main Results:

• Calculated T(1) values showed close agreement with experimental data across three frequencies.
• The model accurately described differences in T(1) for carbons in base pairs, sugar, and backbone, particularly at high frequencies.
• Both second- and first-order theories provided good agreement with experimental findings.

Conclusions:

• The atomistic calculations effectively capture the local dynamics of fluctuating three-dimensional DNA structures.
• The methodology is broadly applicable to other complex biological molecules like proteins and protein-DNA complexes.
• This approach provides a molecular basis for understanding the dynamics of biological macromolecules.