Hierarchical Biomolecular Dynamics: Picosecond Hydrogen Bonding Regulates Microsecond Conformational Transitions

Area of Science:

• Biophysics
• Computational Chemistry
• Structural Biology

Background:

• Biomolecules display structural dynamics across diverse timescales, from picoseconds (ps) to microseconds (μs).
• Nonlinear coupling exists between fast and slow molecular motions, where rapid fluctuations are crucial for slower functional processes.

Purpose of the Study:

• To elucidate the microscopic mechanism underlying multiscale dynamics in biomolecules.
• To investigate the hierarchical coupling of fast and slow structural dynamics using a model system.

Main Methods:

• Extensive molecular dynamics simulations were performed.
• Principal component analysis techniques were employed to analyze simulation data.
• The Aib peptide was utilized as a model system to study hierarchical dynamics.

Main Results:

• A three-tiered free energy landscape was identified in the Aib peptide.
• Dynamics were characterized by chiral transitions (μs), residue conformational changes (ns), and hydrogen bond rearrangements (ps).
• Fast hydrogen bond dynamics were found to be a prerequisite for local conformational transitions, which in turn enable global rearrangements.

Conclusions:

• A hierarchical dynamic mechanism explains the multiscale behavior of biomolecules.
• Fast hydrogen bond dynamics are essential for enabling slower conformational changes.
• The hierarchical coupling results in similar temperature dependencies across different dynamic processes, suggesting a dynamic transition.