Speed of conformational change: comparing explicit and implicit solvent molecular dynamics simulations.

Area of Science:

• Computational Chemistry
• Molecular Dynamics Simulations
• Biophysics

Background:

• Achieving adequate sampling of conformational space in atomistic simulations is computationally demanding, particularly with explicit solvent models.
• Implicit-solvent models offer a potential solution for accelerating conformational sampling in molecular simulations.

Purpose of the Study:

• To systematically compare the conformational sampling speed of generalized Born (GB) implicit-solvent simulations against particle mesh Ewald (PME) explicit-solvent simulations.
• To investigate the impact of system size, conformational change type, and simulation parameters on the relative efficiency of implicit versus explicit solvent models.

Main Methods:

• Atomistic simulations were performed using both PME explicit solvent (TIP3P water) and GB implicit solvent models within the AMBER package.
• Conformational sampling speed was evaluated for small (dihedral flips), large (nucleosome, DNA unwrapping), and mixed (miniprotein folding) events.
• Simulations ranged from nanoseconds to microseconds, with analyses considering temperature effects and solvent viscosity (Langevin collision frequency).

Main Results:

• Generalized Born implicit-solvent simulations demonstrated significant speedups over PME explicit-solvent simulations, ranging from ~1-fold to ~100-fold depending on the system and conformational change.
• Speedups were generally greater for larger and more complex conformational changes.
• Conformational sampling speedup increased with decreasing effective solvent viscosity (Langevin collision frequency) and was primarily attributed to this viscosity reduction.

Conclusions:

• Implicit-solvent models, specifically GB, can substantially accelerate conformational sampling in molecular dynamics simulations compared to explicit solvent (PME).
• The degree of speedup is highly dependent on the system studied and the nature of the conformational change, with larger changes benefiting more.
• Reduced solvent viscosity in implicit-solvent models is the primary driver for enhanced conformational sampling efficiency.