How flexible is a DNA duplex ? An investigation by NMR relaxometry and molecular dynamics simulations

Nucleic acids are central to many bio-molecular processes central to cellular life, yet characterising their molecular motions and fluctuations with atomic resolution can be challenging. To tackle this, we introduce high resolution relaxometry, combined with high field nuclear spin relaxation as a powerful tool to probe the motions. With this approach we identify motions occurring both on the picosecond and low nanosecond time-scales. By integrating these results with molecular dynamics simulations and ensembles, obtained from residual dipolar coupling (RDC) measurements, we can identify which timescales helical motions and sugar puckering dynamics occur on. The approach outlined in this study provides a framework for interrogating molecular dynamics in nucleic acids and benchmarking approaches, such as molecular dynamics simulations, that aim to characterise dynamic processes.