Protonation of DMPC in a Bilayer Environment Using a Linear Response Approximation

Area of Science:

• Biochemistry
• Computational Biology
• Membrane Biophysics

Background:

• pH significantly impacts biomolecules like proteins, nucleic acids, and lipids.
• Computational studies on pH effects have focused on proteins, neglecting lipids in their native bilayer environment.
• Simulating lipid bilayers presents technical challenges due to their periodic nature.

Purpose of the Study:

• To develop a computational method for studying pH effects on lipid bilayers, considering periodic boundary conditions.
• To calculate the pKa of dimyristoylphosphatidylcholine (DMPC) within a zwitterionic lipid bilayer.
• To understand the conformational impact of DMPC protonation on membrane structure.

Main Methods:

• Development of a Poisson-Boltzmann-based method incorporating periodic boundary conditions for lipid bilayers.
• Application of a linear response approximation to calculate pKa values.
• Simulation of DMPC molecules within a zwitterionic lipid environment.

Main Results:

• DMPC protonation is significant only at low pH values (pH 2-3).
• Protonation of DMPC leads to substantial changes in lipid conformations.
• The process induces significant heterogeneity within the lipid membrane.

Conclusions:

• The developed Poisson-Boltzmann method effectively simulates pH effects in periodic lipid bilayer systems.
• DMPC protonation, though occurring at extreme pH, profoundly influences membrane structure and dynamics.
• This work highlights the importance of considering pH in lipid behavior and membrane function.