Biophysics

Free energy analyses of cell penetrating peptides using the weighted ensemble method

Cell penetrating peptides (CPPs) have been widely used for drug-delivery agents, however, it has not been fully understood how they translocate across cell membranes. The Weighted Ensemble (WE) method, one of powerful and flexible path sampling …

Enhancement of direct membrane penetration of cell-penetrating peptides (CPPs) by polyprolines

The transport mechanism of cell-penetrating peptides (CPPs) has not been fully understood and there seems no general rule to design more efficient CPPs. Recent experimental results show that a polyproline-containing arginine-rich peptide efficiently …

Molecular dynamics studies of interactions between Arg9(nona-arginine) and a DOPC/DOPG(4:1) membrane

It has been known that the uptake mechanisms of cell-penetrating peptides (CPPs) depend on the experimental conditions such as the concentration of peptides, lipid composition, and temperature. In this study, we investigate the temperature dependence …

Stochastic steps in secondary active sugar transport

Secondary active transporters, such as those that adopt the leucine-transporter fold, are found in all domains of life, and they have the unique capability of harnessing the energy stored in ion gradients to accumulate small molecules essential for …

Structural determinants of water permeation through the sodium-galactose transporter vSGLT

Sodium-glucose transporters (SGLTs) facilitate the movement of water across the cell membrane, playing a central role in cellular homeostasis. Here, we present a detailed analysis of the mechanism of water permeation through the inward-facing state …

Energetics of Urea Permeation through Sodium-Dependent Galactose Cotransporter vSGLT

In human kidneys, the glomeruli filter about 54 g of urea from the blood each day and approximately 12-14 g of which is reabsorbed in the proximal tubule that is believed to be devoid of urea channels or uniporters. Experimental evidence suggests …

Insight into the Mechanism of Water Permeation through the Sodium-Galactose Transporter vSGLT from Long Molecular Dynamics Simulations

Sodium-glucose transporters (SGLTs) mediate sugar transport as well as water flow across the cell membrane. Using a series of long molecular dynamics simulations generated on the special-purpose Anton supercomputer totaling nearly 16 microseconds in …

Understanding Substrate Unbinding from the Sodium-Galactose Co-Transporter vSGLT based on 16 Microseconds of Molecular Simulation

We report the results from 16 microseconds of molecular dynamics (MD) simulations carried out on vSGLT using the Anton supercomputer at the Pittsburgh Supercomputing Center. We observed multiple galactose unbinding events as well as instances in …

Water Permeation Through the Sodium-Dependent Galactose Cotransporter vSGLT

It is well accepted that cotransporters facilitate water movement by two independent mechanisms: osmotic flow through a water channel in the protein and flow driven by ion/substrate cotransport. However, the molecular mechanism of transport-linked …

The mechanism of sodium and substrate release from the binding pocket of vSGLT

Membrane co-transport proteins that use a five-helix inverted repeat motif have recently emerged as one of the largest structural classes of secondary active transporters1,2. However, despite many structural advances there is no clear evidence of how …