July 2015

Ion channels catalyze ionic permeation across membranes via water-filled pores. To understand how changes in intracellular magnesium concentration regulate the influx of Mg2+ into cells, we examine early events in the relaxation of Mg2+ channel CorA toward its open state using massively-repeated molecular dynamics simulations conducted either with or without regulatory ions. The pore of CorA contains a 2-nm-long hydrophobic bottleneck which remained dehydrated in most simulations. However, rapid hydration or "wetting" events concurrent with small-amplitude fluctuations in pore diameter occurred spontaneously and reversibly. In the absence of regulatory ions, wetting transitions are more likely and include a wet state that is significantly more stable and more hydrated. The free energy profile for Mg2+ permeation presents a barrier whose magnitude is anticorrelated to pore diameter and the extent of hydrophobic hydration. These findings support an allosteric mechanism whereby wetting of a hydrophobic gate couples changes in intracellular magnesium concentration to the onset of ionic conduction. Pomès et al.

Image Credit: Règis Pomès

Editorial

From “What Is?” to “What Isn't?” Computational Biology

Ruth Nussinov, Sebastian Bonhoeffer, Jason A. Papin, Olaf Sporns

PLOS Computational Biology: published July 2, 2015 | https://doi.org/10.1371/journal.pcbi.1004318

Review

Inferring Pairwise Interactions from Biological Data Using Maximum-Entropy Probability Models

Richard R. Stein, Debora S. Marks, Chris Sander

PLOS Computational Biology: published July 30, 2015 | https://doi.org/10.1371/journal.pcbi.1004182

Research Articles

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Spike-Triggered Covariance Analysis Reveals Phenomenological Diversity of Contrast Adaptation in the Retina

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Optimal Prediction of Moving Sound Source Direction in the Owl

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Forecasting Influenza Epidemics in Hong Kong

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Fast Simulation of Mechanical Heterogeneity in the Electrically Asynchronous Heart Using the MultiPatch Module

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Neutral Models of Microbiome Evolution

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Hydrophobic Gating of Ion Permeation in Magnesium Channel CorA

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Markov State Models Reveal a Two-Step Mechanism of miRNA Loading into the Human Argonaute Protein: Selective Binding followed by Structural Re-arrangement

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Emergence of Slow-Switching Assemblies in Structured Neuronal Networks

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Hydrophobic Gating of Ion Permeation in Magnesium Channel CorA

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