Hybrid neMD/MC lipid swapping algorithm to equilibrate membrane simulation with thermodynamic reservoir

Area of Science:

• Computational biology
• Biophysics
• Membrane biophysics

Background:

• Molecular dynamics (MD) simulations are crucial for studying biological membranes.
• Simulating membranes with low-abundance lipids is computationally challenging due to system size and lipid affinity issues.
• Current methods struggle to accurately represent lipid fluctuations and equilibrium in all-atom simulations.

Purpose of the Study:

• To develop a computationally efficient method for simulating biological membranes with diverse lipid compositions.
• To address the challenges of simulating low-abundance lipids in all-atom molecular dynamics.
• To enable accurate modeling of lipid exchange and equilibrium in complex membrane systems.

Main Methods:

• A hybrid non-equilibrium molecular dynamics (neMD)-Monte Carlo (MC) algorithm was developed.
• The algorithm involves swapping lipids between a simulated system and a thermodynamic reservoir.
• Short non-equilibrium trajectories are used to generate new states, followed by Metropolis MC acceptance/rejection.

Main Results:

• The proposed neMD/MC algorithm facilitates natural fluctuation of lipid numbers in simulated systems.
• It effectively simulates systems with desired mole fractions of lipid components, including low-abundance ones.
• The method was tested on phosphatidylcholine and phosphatidylglycerol lipid mixtures, demonstrating its applicability.

Conclusions:

• The neMD/MC algorithm provides a practical and computationally feasible approach for simulating complex biological membranes.
• This method overcomes limitations of traditional MD and MC techniques for systems with low-abundance lipids.
• It enables more accurate studies of membrane structure and dynamics, particularly concerning lipid heterogeneity.