310-Helix Conformation Facilitates the Transition of a Voltage Sensor S4 Segment toward the Down State

AbstractThe activation of voltage-gated ion channels is controlled by the S4 helix, with arginines every third residue. The x-ray structures are believed to reflect an open-inactivated state, and models propose combinations of translation, rotation, and tilt to reach the resting state. Recently, experiments and simulations have independently observed occurrence of 310-helix in S4. This suggests S4 might make a transition from α- to 310-helix in the gating process. Here, we show 310-helix structure between Q1 and R3 in the S4 segment of a voltage sensor appears to facilitate the early stage of the motion toward a down state. We use multiple microsecond-steered molecular simulations to calculate the work required for translating S4 both as α-helix and transformed to 310-helix. The barrier appears to be caused by salt-bridge reformation simultaneous to R4 passing the F233 hydrophobic lock, and it is almost a factor-two lower with 310-helix. The latter facilitates translation because R2/R3 line up to face E183/E226, which reduces the requirement to rotate S4. This is also reflected in a lower root mean-square deviation distortion of the rest of the voltage sensor. This supports the 310 hypothesis, and could explain some of the differences between the open-inactivated- versus activated-states

Steady moving contact line of water over a no-slip substrate

The movement of the triple contact line plays a crucial role in many applications such as ink-jet printing, liquid coating and drainage (imbibition) in porous media. To design accurate computational tools for these applications, predictive models of the moving contact line are needed. However, the basic mechanisms responsible for movement of the triple contact line are not well understood but still debated. We investigate the movement of the contact line between water, vapour and a silica-like solid surface under steady conditions in low capillary number regime. We use molecular dynamics (MD) with an atomistic water model to simulate a nanoscopic drop between two moving plates. We include hydrogen bonding between the water molecules and the solid substrate, which leads to a sub-molecular slip length. We benchmark two continuum methods, the Cahn-Hilliard phase-field (PF) model and a volume-of-fluid (VOF) model, against MD results. We show that both continuum models can reproduce the statistical measures obtained from MD reasonably well, with a trade-off in accuracy. We demonstrate the importance of the phase field mobility parameter and the local slip length in accurately modelling the moving contact line.Comment: 26 pages, 13 figures, 4 tables, post-review version, under consideration for publication in "European Physical Journal Special Topics

GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers

AbstractGROMACS is one of the most widely used open-source and free software codes in chemistry, used primarily for dynamical simulations of biomolecules. It provides a rich set of calculation types, preparation and analysis tools. Several advanced techniques for free-energy calculations are supported. In version 5, it reaches new performance heights, through several new and enhanced parallelization algorithms. These work on every level; SIMD registers inside cores, multithreading, heterogeneous CPU–GPU acceleration, state-of-the-art 3D domain decomposition, and ensemble-level parallelization through built-in replica exchange and the separate Copernicus framework. The latest best-in-class compressed trajectory storage format is supported