Jinhui Li

PhD Candidate
Viviana Monje Research Group

Asymmetric Permeation Path of the Glycoside Compound Through Lipid Bilayers

Abstract

Saponins, an important class of glycoside compounds, receive extensive attention for their potential medicinal value. Recent studies found that passive permeation is the primary pathway for saponins to cross various cell membranes, modulating their biological activities. Here, we employed transition-tempered metadynamics to study the permeation of a model saponin (SA). The simulation results revealed the asymmetric SA permeation mechanism and membrane defects caused by the permeation. We also applied the dimensionality reduction technique, i.e., (tICA), to design a new CV set. This new CV set can increase the sampling efficiency without lowering the accuracy of free energy surface. Finally, we predicted SA's permeability based on the inhomogeneous solubility diffusion model. The comparison with experimental data showed an obvious improvement compared to similar simulation studies. In conclusion, this work provides atomistic insights into the permeation of saponin compounds and offers a systematic simulation scheme for studying other potential drug molecules.