Sampling the Grand Canonical Ensemble with Multisite λ Dynamics

Area of Science:

• Computational chemistry
• Molecular dynamics
• Biophysics

Background:

• Grand canonical ensemble simulations are crucial for studying molecular systems.
• Existing methods like GCMC/MD can be computationally intensive.
• Accurate simulation of molecular fluctuations is key in various scientific domains.

Purpose of the Study:

• To develop a novel molecular simulation technique, grand canonical multisite lambda dynamics (GC-MSλD).
• To enable efficient sampling of molecular number fluctuations and control chemical potential.
• To provide a potentially faster and less computationally demanding alternative to existing methods.

Main Methods:

• Coupling molecules of interest to a dynamic lambda (λ) variable.
• Utilizing a λ-dependent energetic bias to control chemical potential and molecular number.
• Implementing and demonstrating the GC-MSλD framework in molecular simulations.

Main Results:

• Successfully demonstrated GC-MSλD for controlling molecular numbers in TIP3P water.
• Applied the method to sample crystallographic water occupancies within protein cavities.
• Computed protein-ligand binding free energies, including water displacement effects.

Conclusions:

• GC-MSλD offers a promising new approach for molecular simulations.
• The method shows potential for faster equilibration and reduced computational cost.
• GC-MSλD is applicable to complex biological systems, including protein-ligand interactions and water dynamics.