Molecular Insight into Affinities of Gallated and Nongallated Proanthocyanidins Dimers to Lipid Bilayers

Abstract

Experimental studies have proved the beneficial effects of proanthocyanidins (Pas) relating to interaction with the cell membrane. But the detailed mechanisms and structure-function relationship was unclear. In present study, molecular dynamics (MD) simulations were used to study the interactions of four PA dimers with a lipid bilayer composed of 1:1 mixed 1-palmitoyl-2-oleoyl phosphatidylcholine (POPC) and 1-palmitoyl-2-oleoyl phosphatidylethanolamine (POPE). The results showed that the gallated PA dimers had much higher affinities to the bilayer with lower binding free energies compared with nongallated PA dimers. The gallated PA dimers penetrated deeper into the bilayer and formed more hydrogen bonds (H-bonds) with bilayer oxygen atoms, especially the deeper oxygen atoms of the lipids simultaneously, thus inducing stronger lateral expansion of the membrane and lipid tails disorder. The present results provided molecular insights into the interactions between PA dimers and bio-membranes and agreed with our experimental results well. These molecular interactions helped to elucidate the structure-function relationship of the PA dimers and provided a foundation for a better understanding of the underlying mechanisms of the bioactivities of PA oligomers.

Mechanistic Understanding from Molecular Dynamics in Pharmaceutical Research 2: Lipid Membrane in Drug Design

“…Phenolic compounds Artepillin C [460], Chlorogenic acid and Isochlorogenic acid [461], Proanthocyanidins [462,463], Oleuropein aglycone [464], Other [465][466][467][468][469] The orientation and location of drug molecules in lipid membranes is clearly only the beginning of our story. Once molecules enter a biomembrane they can do three different things: (1) pass out of the membrane again, possibly on the other side, the membrane merely forming a biological barrier on their way to their eventual destination, (2) act collectively to instigate large scale alteration or even disruption of the membrane structure, or (3) interact with proteins that are associated with the membrane.…”

Health-Promoting Properties of Proanthocyanidins for Intestinal Dysfunction

“…Thus, PACs not only alter enzymatic activity, but they may also prevent ligand-receptor interactions and the binding of transcription factors to their specific sites in DNA. In addition, some PAC molecules can be adsorbed non-specifically onto biomembrane surfaces [149], affecting their physical characteristics, such as fluidity and density, and potentially altering membrane-dependent processes, including protein receptor activity [150]. Altogether, these effects lead ultimately to the alteration of cell signaling pathways and the modulation of gene expression ( Figure 3).…”

Beneficial Effects of Proanthocyanidins on Intestinal Permeability and Its Relationship with Inflammation

“…Thus, PACs not only alter enzymatic activity, but they may also prevent ligand-receptor interactions and the binding of transcription factors to their specific sites in DNA. In addition, some PAC molecules can be adsorbed non-specifically onto biomembrane surfaces [118], affecting their physical characteristics, such as fluidity and density, and potentially altering membrane-dependent processes, including protein receptor activity [119]. Altogether, these effects lead ultimately to the alteration of cell signaling pathways and the modulation of gene expression.…”