Molecular rigidity and enthalpy-entropy compensation in DNA melting

Area of Science:

• Molecular Physics
• Biophysics
• Computational Chemistry

Background:

• Enthalpy-entropy compensation (EEC) is a widespread phenomenon in molecular binding processes relevant to biology and manufacturing.
• A clear molecular physics understanding of EEC, particularly in DNA systems, remains elusive.
• Previous studies suggest a link between EEC and molecular rigidity in binding-unbinding events.

Purpose of the Study:

• To investigate the relationship between molecular rigidity and enthalpy-entropy compensation (EEC) in double-stranded DNA (dsDNA) melting.
• To explore how intrinsic and extrinsic factors affecting DNA rigidity influence binding thermodynamics.
• To provide a molecular-level insight into the origins of EEC in complex molecular systems.

Main Methods:

• Utilized coarse-grained molecular dynamics simulations to model dsDNA melting.
• Quantified DNA molecular rigidity under various conditions, including changes in base association strength, chain length, and bending stiffness.
• Investigated the impact of external factors like polymer additives and geometrical confinement on DNA rigidity and binding thermodynamics.

Main Results:

• Confirmed EEC in all simulated dsDNA melting scenarios, strongly correlating it with changes in molecular rigidity.
• Identified two distinct patterns: increased intrinsic DNA rigidity enhanced binding entropy, while externally constrained rigidity decreased it.
• Demonstrated that variations in dsDNA rigidity, both intrinsic and extrinsic, directly impact enthalpy and entropy of binding.

Conclusions:

• Molecular rigidity plays a crucial role in enthalpy-entropy compensation (EEC) during DNA melting.
• The influence of rigidity on binding entropy depends on whether the rigidity is intrinsic or externally imposed.
• Changes in molecular rigidity may represent a common underlying mechanism for the ubiquitous EEC phenomenon observed in diverse binding processes.