A UNITED-ATOM REPRESENTATION FOR SPHINGOLIPIDS IN THE CHARMM MOLECULAR DYNAMICS FORCE FIELD

Abstract

The development of the CHARMM force field (FF) in the late 1970’s and early 1980’s was groundbreaking at the time. For the first time, a computer program was created that could simulate biological systems on a macromolecular scale. Starting with the simulation of simple proteins, CHARMM has since expanded to include such macromolecules as nucleic acids and lipids, now being able to model complex biological systems and processes. Force fields like CHARMM can be represented in different ways. For example, force fields can be represented through an all-atom representation, in which all atoms in a system are modeled as distinct interaction units. This representation can be simplified into a united-atom representation, which shall be the primary focus of this thesis. A united atom FF has no explicit interaction sites for hydrogen. Instead, the hydrogens are lumped onto the atoms they are connected to, termed ‘heavy atoms’ as these atoms have a greater atomic weight than hydrogen. The CHARMM FF originally had a united-atom representation for proteins, which was abandoned to focus on all-atom representations. However, in certain cases, such as lipid tails, united-atom representations are often useful in certain situations; as compared to all-atom representations, united-atom models often speed up simulation times, which is useful in the simulation of large enough systems of molecules. Although there are currently united-atom representations for many types of biomolecules in the CHARMM FF, including multiple types of membrane lipids, there has yet to be a united-atom model for sphingolipids, a type of membrane lipid most commonly found in the myelin sheath of neurons, although its presence has been noted in many types of eukaryotic cells. The goal of this thesis is thus to develop such a model and implement it in the CHARMM FF.