Configurational Sampling of All-Atom Solvated Membranes Using Hybrid Nonequilibrium Molecular Dynamics Monte Carlo...

Area of Science:

• Biophysics
• Computational Biology
• Membrane Biophysics

Background:

• All-atom simulations are crucial for studying biological membrane structure and dynamics.
• Sampling atomic configurations in inhomogeneous membranes is computationally challenging due to slow lipid diffusion.

Purpose of the Study:

• To develop an efficient simulation method for sampling lipid configurations in inhomogeneous biological membranes.
• To overcome the limitations of slow lateral diffusion in traditional molecular dynamics simulations.

Main Methods:

• A hybrid nonequilibrium molecular dynamics Monte Carlo (neMD/MC) simulation approach was developed.
• Random lipid molecule swaps were performed, with acceptance/rejection based on Metropolis criterion and alchemical work calculated via short trajectories.
• A dual-topology framework constrained common atoms of exchanging molecules.

Main Results:

• The neMD/MC method achieved good acceptance probability with short switching trajectories (10 ps).
• The algorithm effectively sampled lipid distributions near a charged transmembrane helix.
• Demonstrated efficient sampling for a binary mixture of charged and zwitterionic lipids.

Conclusions:

• The proposed hybrid neMD/MC simulation method significantly enhances the sampling efficiency of lipid configurations in biological membranes.
• This approach provides a powerful tool for studying membrane heterogeneity and lipid-protein interactions, particularly in systems with charged components.