CHARMM FORCE FIELD PARAMETERIZATION OF BACTERIAL LIPOPOLYSACCHARIDES

A Moraru and I Svab and DF Mihailescu, REVUE ROUMAINE DE CHIMIE, 54, 799-+ (2009).

Bacterial lipopolysaccharides (LPS) are major components of the Gram- negative bacteria outer membrane and arc known to trigger a variety of inflammatory reactions in macrophages and other cells presenting a CD14 receptor. LPS consist of a hydrophobic domain known as lipid A (or endotoxin), a nonrepeating "core" oligosaccharide and a distal polysaccharide (or O-antigen). The purpose of this study was to obtain the parameters of the LPS molecule consistent with force fields that use an atomic detailed description of structure and dynamics like CHARMM and NAMD. The parameters for the lipid A region were determined de novo. All the quantum chemical calculations for this molecule were completed using the Gaussian03 software at the Restricted Hartree Fock (RHF) level of theory using the Pople 6-31G* basis set. The nonbonded terms, namely the van der Waals term and the electrostatic term, were available in the CHARMM force field and therefore were assigned by analogy. The "core" oligosaccharide contains unusual sugars with seven or eight carbon atoms. This structure was built using a patching method for which a flexible topology file was determined using VMD extension Molefacture. In our study we determined a set of parameters for the LPS molecule to be further used in molecular modeling simulations with CHAPMM force field. These results can be easily adapted by the user to model different LPS molecules.

Return to Publications page