TY - JOUR

T1 - Intermolecular Voids in Lipid Bilayers in the Presence of Glycyrrhizic Acid

AU - Shelepova, Ekaterina A.

AU - Kim, Alexandra V.

AU - Voloshin, Vladimir P.

AU - Medvedev, Nikolai N.

PY - 2018/11/1

Y1 - 2018/11/1

N2 - It is known that glycyrrhizic acid (GA) promotes the enhancement of the activity of several medicines. This is attributed to the fact that GA increases the membrane permeability of small drug molecules. There is an opinion that GA facilitates the formation of additional large voids in the membrane, which enhance the passive diffusion of molecules across the membrane. In this work, we investigate how GA influences the intermolecular voids using the molecular dynamics simulation. We calculate the interstitial spheres (empty spheres inscribed between molecules) in model DPPC and DOPC bilayers, both pure and with the addition of cholesterol. It was observed that the addition of GA does not lead to the formation of new large interstitial spheres; i.e., new large voids do not appear. The distribution of empty volume inside the bilayers is also studied. We calculated the profiles of the empty volume fraction both from the middle plane of the bilayer and from its outer surface (from the lipid-water interface). This analysis has shown that the addition of GA does not cause the increase of the empty volume in the bilayer; moreover, there is a slight decrease in the bilayers with cholesterol. Thus, we have not found a confirmation of the simplest hypothesis that individual GA molecules induce pores in the membrane.

AB - It is known that glycyrrhizic acid (GA) promotes the enhancement of the activity of several medicines. This is attributed to the fact that GA increases the membrane permeability of small drug molecules. There is an opinion that GA facilitates the formation of additional large voids in the membrane, which enhance the passive diffusion of molecules across the membrane. In this work, we investigate how GA influences the intermolecular voids using the molecular dynamics simulation. We calculate the interstitial spheres (empty spheres inscribed between molecules) in model DPPC and DOPC bilayers, both pure and with the addition of cholesterol. It was observed that the addition of GA does not lead to the formation of new large interstitial spheres; i.e., new large voids do not appear. The distribution of empty volume inside the bilayers is also studied. We calculated the profiles of the empty volume fraction both from the middle plane of the bilayer and from its outer surface (from the lipid-water interface). This analysis has shown that the addition of GA does not cause the increase of the empty volume in the bilayer; moreover, there is a slight decrease in the bilayers with cholesterol. Thus, we have not found a confirmation of the simplest hypothesis that individual GA molecules induce pores in the membrane.

KW - MOLECULAR-DYNAMICS SIMULATIONS

KW - TRITERPENOID SAPONINS

KW - PHOSPHOLIPID-MEMBRANES

KW - CELL-MEMBRANES

KW - PERMEABILITY

KW - CHOLESTEROL

KW - SYSTEMS

KW - DISTRIBUTIONS

KW - COMPLEXES

KW - ALGORITHM

UR - http://www.scopus.com/inward/record.url?scp=85055144480&partnerID=8YFLogxK

U2 - 10.1021/acs.jpcb.8b07989

DO - 10.1021/acs.jpcb.8b07989

M3 - Article

C2 - 30299964

AN - SCOPUS:85055144480

VL - 122

SP - 9938

EP - 9946

JO - Journal of Physical Chemistry B

JF - Journal of Physical Chemistry B

SN - 1520-6106

IS - 43

ER -