Expanding the CHARMM36 United Atom Chain Model for the Inclusion of Sphingolipids.

Abstract

The inclusion of accurate yet computationally inexpensive lipid force fields (FF) is pertinent for the study of lipids and lipid-containing systems using molecular dynamics (MD). Within the past decade, the implementation and further expansion of a united atom (UA) FF for lipids have been developed in the CHARMM family of FFs. The most recent version of the UA presented more accurate descriptions of lipid properties for several phospholipids with saturated and monounsaturated chains, termed C36UAr. However, the original C36UAr model lacks parameters for an important class of lipids, such as sphingolipids. The focus of this article is to broaden the scope of the C36UAr chain model to incorporate these lipids. In this study, two common sphingolipids, N-palmitoyl sphingomyelin and N-stearoyl sphingomyelin are converted to a UA-chain representation and simulated to investigate the accuracy and speed over the all-atom FF model for sphingolipids. Improvements were found among multiple parameters, for example, in the surface area per lipid (SA/lip) and hydrogen order parameters, over the all-atom simulations of these sphingomyelins in C36, while as much as halving the simulation time for simulations of the same setup otherwise. Thus, the accuracy and efficiency found in this study are consistent with those found in the C36UAr model for phospholipids and expand the application of C36UAr to a wider array of membrane models to better match that in vivo.