Improvement of Parameters of the AMBER Potential Force Field for Phospholipids for Description of Thermal Phase Transitions

Abstract

In this study, we improved parameters of the AMBER potential force field for phospholipids in order to describe the thermal phase transition using molecular dynamic (MD) simulations. To estimate the errors of the main phase transition temperature (<i>T</i>_m), first, MD simulations using the GAFFlipid and Gaff parameters were performed for six phospholipid bilayers, 1,2-dipalmitoyl-<i>sn</i>-glycero-3-phosphocholine (DPPC), 1,2-dipalmitoyl-<i>sn</i>-glycero-3-phosphoethanolamine (DPPE), 1,2-dioleoyl-<i>sn</i>-glycero-3-phosphocholine (DOPC), 1,2-distearoyl-<i>sn</i>-glycero-3-phosphocholine (DSPC), 1-palmitoyl,2-oleoyl-<i>sn</i>-glycero-3-phosphocholine (POPC), and 1-palmitoyl,2-oleoyl-<i>sn</i>-glycero-3-phosphoethanolamine (POPE), with increasing temperature. The <i>T</i>_m values were characterized according to the structural parameter, area per lipid, and gauche ratio in alkyl chains. The <i>T</i>_m values of the six lipids showed ∼50 K differences from the experimentally measured values. To reduce these errors, the well-depth values in the Lennard–Jones potential of the alkyl chains were modified to fit the <i>T</i>_m values of the simulation to the experimental values in a single DPPC bilayer. After the fitting procedure, the <i>T</i>_m values of the six lipids improved, and the errors of <i>T</i>_m improved from ∼50 to ∼15 K. We show that the simulation applying the improved parameters provides more accurate results than the original parameters. These modified parameters were also found to be useful for performing MD simulation of transmembrane proteins with membrane models