Computational conformational analysis of neural membrane lipids:development of force field parameters for phospholipids using semi-empirical molecular orbital calculations

Abstract

MM2 force field parameters for phospholipids were developed. These parameters — MM2(Lipid) — were employed in energy-minimization calculations (using crystal structures as starting conformations) on four phospholipids: dimyristoylphosphatidylglycerol, dilauroylphosphatidyl-N,N-dimethylamine, 1,2-dilauroyl-dl-phosphatidylethanolamine, and deoxylysophosphatidylcholine. After minimization, slight conformational changes were seen in the hydrocarbon chains, while greater change was seen at the head group. The diacylglycerol backbone of the energy-minimized structures exhibited conformations corresponding to experimentally observed conformations. The energy minimization of a randomly and significantly altered geometry of 1,2-dilauroyl-dl-phosphatidylethanolamine resulted in a head group conformation that closely agreed with ab initio theoretical calculations. The utility of AM1 in molecular mechanics parameterization was demonstrated.