Folding and misfolding of potassium channel monomers during assembly and tetramerization.

The dynamics and folding of potassium channel pore domain monomers are connected to the kinetics of tetramer assembly. In all-atom molecular dynamics simulations of Kv1.2 and KcsA channels, monomers adopt multiple nonnative conformations while the three helices remain folded.

CHARMM-GUI Membrane Builder toward realistic biological membrane simulations.

CHARMM-GUI Membrane Builder, http://www.charmm-gui.org/input/membrane, is a web-based user interface designed to interactively build all-atom protein/membrane or membrane-only systems for molecular dynamics simulations through an automated optimized process.

Preferred orientations of phosphoinositides in bilayers and their implications in protein recognition mechanisms.

Phosphoinositides (PIPs), phosphorylated derivatives of phosphatidylinositol (PI), are essential regulatory lipids involved in various cellular processes, including signal transduction, membrane trafficking, and cytoskeletal remodeling. To gain insight into the protein-PIPs recognition process, it is necessary to study the inositol ring orientation (with respect to the membrane) of PIPs with different phosphorylation states. In this study, 8 PIPs (3 PIP, 2 PIP2, and 3 PIP3) with different phosphorylation and protonation sites have been separately simulated in two mixed bilayers (one with 20% phosphatidylserine (PS) lipids and another with PS lipids switched to phosphatidylcholine (PC) lipids), which roughly correspond to yeast membranes.

Glycan Reader: automated sugar identification and simulation preparation for carbohydrates and glycoproteins.

Understanding how glycosylation affects protein structure, dynamics, and function is an emerging and challenging problem in biology. As a first step toward glycan modeling in the context of structural glycobiology, we have developed Glycan Reader and integrated it into the CHARMM-GUI, http://www.charmm-gui.

Orientation of fluorescent lipid analogue BODIPY-PC to probe lipid membrane properties: insights from molecular dynamics simulations.

Single-molecule fluorescence measurements have been used to characterize membrane properties, and recently showed a linear evolution of the fluorescent lipid analogue BODIPY-PC toward small tilt angles in Langmuir-Blodgett monolayers as the lateral surface pressure is increased. In this work, we have performed comparative molecular dynamics (MD) simulations of BODIPY-PC in DPPC (dipalmitoylphosphatidylcholine) monolayers and bilayers at three surface pressures (3, 10, and 40 mN/m) to explore (1) the microscopic correspondence between monolayer and bilayer structures, (2) the fluorophore's position within the membrane, and (3) the microscopic driving forces governing the fluorophore's tilting. The MD simulations reveal very close agreement between the monolayer and bilayer systems in terms of the fluorophore's orientation and lipid chain order, suggesting that monolayer experiments can be used to approximate bilayer systems.