Electronic Polarizability Tunes the Function of the Human Bestrophin 1 Cl Channel.

Mechanisms of anion permeation within ion channels and nanopores remain poorly understood. Recent cryo-electron microscopy structures of the human bestrophin 1 Cl channel (hBest1) provide an opportunity to evaluate ion interactions predicted by molecular dynamics (MD) simulations against experimental observations. Here, we implement the fully polarizable force field AMOEBA in MD simulations on different conformations of hBest1.

Functional dynamics of G protein-coupled receptors reveal new routes for drug discovery.

G protein-coupled receptors (GPCRs) are the largest human membrane protein family that transduce extracellular signals into cellular responses. They are major pharmacological targets, with approximately 26% of marketed drugs targeting GPCRs, primarily at their orthosteric binding site. Despite their prominence, predicting the pharmacological effects of novel GPCR-targeting drugs remains challenging due to the complex functional dynamics of these receptors.

The Role of Cholesterol in M2 Clustering and Viral Budding Explained.

The influenza A M2 homotetrameric channel consists of four transmembrane (TM) and four amphipathic helices (AHs). This viral proton channel is suggested to form clusters in the catenoid budding neck areas in raft-like domains of the plasma membrane, resulting in cell membrane scission and viral release. The channel clustering environment is rich in cholesterol.

Molecular mechanism of anion permeation through aquaporin 6.

Aquaporins (AQPs) are recognized as transmembrane water channels that facilitate selective water permeation through their monomeric pores. Among the AQP family, AQP6 has an intriguing characteristic as an anion channel, which is allosterically controlled by pH conditions and is eliminated by a single amino acid mutation. However, the molecular mechanism of anion permeation through AQP6 remains unclear.

Mapping structural and dynamic divergence across the MBOAT family.

Membrane-bound O-acyltransferases (MBOATs) are membrane-embedded enzymes that catalyze acyl chain transfer to a diverse group of substrates, including lipids, small molecules, and proteins. MBOATs share a conserved structural core, despite wide-ranging functional specificity across both prokaryotes and eukaryotes. The structural basis of catalytic specificity, regulation and interactions with the surrounding environment remain uncertain.