Ab Initio and Semiempirical Conformation Potentials for Phospholipid Head Groups

Abstract

The conformational potential of the dimethyl phosphate (DMP) anion and the 2-ammonioethanol (AME) cation, which are substructures of the phosphoethanolamine head group of phospholipids, has been investigated at the Hartree-Fock (HF) level using the 3-21G, 3-21G(*), 6-31G*, and 6-31+G* basis set. For this purpose, both the DMP anion and the AME cation were considered as geminal double rotors with the two rotor groups OCH3 in the case of DMP and OH and CH2NH3+ in the case of AME. Extensive scans (17 points including eight stationary points for DMP and 30 points including seven stationary points for AME) of the conformational energy surface were carried out by complete geometry optimizations at the HF/3-21G and HF/3-21G(*) levels, respectively, and subsequent single point calculations with larger basis sets. The most stable DMP form has the two OCH3 groups in syn-clinal (+sc) positions (both dihedral angles a 2 and a 3 = 75.3') while the AME cation prefers an anti-periplanar (ap) (Q = 173.3'), syn-clinal (+sc) (a5 = 48.5') conformation with regard to the OH and CH2NH3+ groups. The DMP anion is a rather flexible rotor that can undergo various flip-flop rotations (barriers 1 and 6 kcal/mol) that indicate strong coupling between the rotor groups. The AME cation, on the other hand, is conformationally not flexible, which has to do with the fact that the two rotor groups OH and CH2NH3+ are electronically very different. The preferred rotational processes of the AME cation involve inwardly or outwardly directed rotations at the CC bond (barriers of 5.1 and 9.3 kcaymol) with the OH group kept essentially in an ap position. Calculations reveal that semiempirical methods such as PM3 are not able to describe the conformational tendencies of either DMP anion or AME cation correctly.

Hybrid QM/MM simulation of the hydration phenomena of dipalmitoylphosphatidylcholine headgroup

“…In many previous quantum mechanical researches, it is shown that the polar headgroups of the phospholipids manifest an intrinsic preference towards folded structures stabilized by strong intramolecular hydrogen bonds (Fig. 1) or electrostatic interaction between the phosphate group and the cationic head in gas phase [3,5,9]. X-ray experimental studies [14] also indicate that the polar headgroups * Corresponding author.…”

“…Some properties of biological membranes can be directly attributed to the characteristics of single phospholipid molecules. Due to their important role, phospholipids are the subject of numerous experimental and computational studies in recent decades [2][3][4][5][6][7][8].…”

“…In many previous works [3,5,[9][10][11][12][13], a detailed structural knowledge of the biological membrane is particularly associated with the conformation and interactions of polar phospholipid headgroups at the membrane surface. In many previous quantum mechanical researches, it is shown that the polar headgroups of the phospholipids manifest an intrinsic preference towards folded structures stabilized by strong intramolecular hydrogen bonds (Fig.…”

“…Although there are numerous previous computational studies [3,5,[9][10][11][12][13], which analyzed the structure and hydration of phospholipid headgroup. Considering the limits of computing ability, the majority of these investigations have used short chain molecules (e.g.…”

Crystal structure and molecular stereochemistry of polymeric Cu2(DMP)4(DMSO) as a platform for phosphate diester binding

“…* and a large body of other works [41][42]. These studies and also Monte-Carlo simulations of aqueous solvation of DMP [43][44] have shown that the (gg) conformer to be the most stable, followed by (gt) and (tt) conformations.…”