Molecular Dynamic Studies on Organelle-Specific Yeast Membrane Models and Amphipathic Lipid Packing Sensor Motif Binding Mechanism

Abstract

The present study analyzes improved computational membrane models for specific organelles in yeast. Previous molecular dynamic (MD) simulations were performed on yeast membrane models having six lipid types with lipid composition averages between the endoplasmic reticulum (ER) and the plasma membrane (PM) (BJ. 97:50-58). The models studied in this research include ergosterol (ERG), phosphatidic acid (PA), phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS), and phosphatidylinositol (PI) lipids, with bilayer diversity ranging between six and eleven lipid types. MD simulations were used to equilibrate systems with lipid compositions characteristic to the ER, PM, and Golgi network (TGN) membranes. Data analysis provided better understanding of membrane behavior, mechanical properties, order parameters, electron density profiles (EDPs), and lipid packing. Selected models will be used to advance the study of peripheral membrane Osh4 binding mechanism and function. The ALPS-like motif, a peptide from Osh4, was previously identified in our lab as a recurring portion of the protein involved in the binding process (JMB243:847-862). The binding mechanism of ALPS to DOPC bilayers was studied with MD simulations of at least 200ns. All simulations were carried with the NPT ensemble, but simulations in the constant surface tension ensemble (NPγT) were also run with the bilayer-peptide systems at varying values for γ.