Molecular dynamics based enhanced sampling of collective variables with very large time steps

Area of Science:

• Computational molecular sciences
• Physical chemistry
• Molecular dynamics simulations

Background:

• Enhanced sampling techniques are crucial for exploring free-energy landscapes in complex systems.
• Molecular dynamics (MD) simulations are limited by time steps constrained by fast system motions.
• Standard multiple time-stepping methods face limitations due to resonance phenomena coupling fast and slow motions.

Purpose of the Study:

• To adapt resonance-free multiple time-step algorithms for enhanced sampling techniques.
• To enable larger time steps in simulations employing adiabatic free-energy dynamics, unified free-energy dynamics, and metadynamics.
• To improve the efficiency of conformational exploration in computational studies.

Main Methods:

• Development and application of deterministic and stochastic resonance-free multiple time-step algorithms.
• Imposition of isokinetic constraints coupling the physical system to Nosé-Hoover chains or Nosé-Hoover Langevin schemes.
• Integration of these algorithms with collective variable-based enhanced sampling methods.

Main Results:

• Achieved ten- to twenty-fold gains in large time steps compared to standard methods.
• Successfully adapted resonance-free integrators for enhanced sampling techniques.
• Demonstrated significant improvements in simulation efficiency for conformational exploration.

Conclusions:

• Resonance-free multiple time-step integrators effectively overcome limitations in standard methods.
• The integration with enhanced sampling techniques significantly boosts computational efficiency.
• These advancements facilitate more extensive exploration of free-energy landscapes.