Local dynamics coupled to hydration water determines DNA-sequence-dependent deformability

Area of Science:

• Biophysics
• Computational Biology
• Structural Biology

Background:

• DNA deformability and dynamics are crucial for biological functions.
• Hydration water plays a significant role in DNA structural transitions.
• Understanding sequence-dependent DNA dynamics is key to predicting its behavior.

Purpose of the Study:

• To investigate the sequence-dependent dynamics of hydrated DNA dodecamers.
• To correlate DNA base pair step dynamics with hydration water interactions.
• To elucidate the relationship between DNA deformability and local dynamics.

Main Methods:

• Molecular dynamics (MD) simulations were performed on two DNA dodecamers with differing flexibility.
• Quasielastic neutron scattering (QENS) experiments were used to probe DNA dynamics.
• Analysis focused on dynamics above the observed dynamical transition temperature (200-240 K).

Main Results:

• Both rigid (AATT) and flexible (TTAA) DNA dodecamers showed a dynamical transition around 200-240 K.
• The AATT sequence exhibited smaller fluctuation amplitude and longer relaxation times compared to TTAA.
• Sequence-dependent DNA base pair step dynamics were observed above the transition temperature and correlated with hydrogen bond breaking with water.

Conclusions:

• DNA deformability is intrinsically linked to the local dynamics of base pair steps.
• These DNA dynamics are coupled to the behavior of hydration water in the minor groove.
• The AT base pair step is kinetically more stable than the TA step, influencing overall DNA flexibility.