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
PLOS Computational Biology: published July 2, 2015 | https://doi.org/10.1371/journal.pcbi.1004318
Related Articles
Review
Inferring Pairwise Interactions from Biological Data Using Maximum-Entropy Probability Models
PLOS Computational Biology: published July 30, 2015 | https://doi.org/10.1371/journal.pcbi.1004182
Research Articles
Asynchronous Rate Chaos in Spiking Neuronal Circuits
PLOS Computational Biology: published July 31, 2015 | https://doi.org/10.1371/journal.pcbi.1004266
Interdomain Contacts Control Native State Switching of RfaH on a Dual-Funneled Landscape
PLOS Computational Biology: published July 31, 2015 | https://doi.org/10.1371/journal.pcbi.1004379
Spike-Triggered Covariance Analysis Reveals Phenomenological Diversity of Contrast Adaptation in the Retina
PLOS Computational Biology: published July 31, 2015 | https://doi.org/10.1371/journal.pcbi.1004425
Optimal Prediction of Moving Sound Source Direction in the Owl
PLOS Computational Biology: published July 30, 2015 | https://doi.org/10.1371/journal.pcbi.1004360
Forecasting Influenza Epidemics in Hong Kong
PLOS Computational Biology: published July 30, 2015 | https://doi.org/10.1371/journal.pcbi.1004383
Learning the Structure of Biomedical Relationships from Unstructured Text
PLOS Computational Biology: published July 28, 2015 | https://doi.org/10.1371/journal.pcbi.1004216
Decreasing-Rate Pruning Optimizes the Construction of Efficient and Robust Distributed Networks
PLOS Computational Biology: published July 28, 2015 | https://doi.org/10.1371/journal.pcbi.1004347
Nullspace Sampling with Holonomic Constraints Reveals Molecular Mechanisms of Protein Gαs
PLOS Computational Biology: published July 28, 2015 | https://doi.org/10.1371/journal.pcbi.1004361
Fast Simulation of Mechanical Heterogeneity in the Electrically Asynchronous Heart Using the MultiPatch Module
PLOS Computational Biology: published July 23, 2015 | https://doi.org/10.1371/journal.pcbi.1004284
Neutral Models of Microbiome Evolution
PLOS Computational Biology: published July 22, 2015 | https://doi.org/10.1371/journal.pcbi.1004365
Timing and Variability of Galactose Metabolic Gene Activation Depend on the Rate of Environmental Change
PLOS Computational Biology: published July 22, 2015 | https://doi.org/10.1371/journal.pcbi.1004399
What Can Interaction Webs Tell Us About Species Roles?
PLOS Computational Biology: published July 21, 2015 | https://doi.org/10.1371/journal.pcbi.1004330
Quantitative Analysis of the Association Angle between T-cell Receptor Vα/Vβ Domains Reveals Important Features for Epitope Recognition
PLOS Computational Biology: published July 17, 2015 | https://doi.org/10.1371/journal.pcbi.1004244
Dynamical Localization of DivL and PleC in the Asymmetric Division Cycle of Caulobacter crescentus: A Theoretical Investigation of Alternative Models
PLOS Computational Biology: published July 17, 2015 | https://doi.org/10.1371/journal.pcbi.1004348
Hydrophobic Gating of Ion Permeation in Magnesium Channel CorA
PLOS Computational Biology: published July 16, 2015 | https://doi.org/10.1371/journal.pcbi.1004303
Identification of Ohnolog Genes Originating from Whole Genome Duplication in Early Vertebrates, Based on Synteny Comparison across Multiple Genomes
PLOS Computational Biology: published July 16, 2015 | https://doi.org/10.1371/journal.pcbi.1004394
Markov State Models Reveal a Two-Step Mechanism of miRNA Loading into the Human Argonaute Protein: Selective Binding followed by Structural Re-arrangement
PLOS Computational Biology: published July 16, 2015 | https://doi.org/10.1371/journal.pcbi.1004404
Emergence of Slow-Switching Assemblies in Structured Neuronal Networks
PLOS Computational Biology: published July 15, 2015 | https://doi.org/10.1371/journal.pcbi.1004196
Related Articles
Adaptive Synaptogenesis Constructs Neural Codes That Benefit Discrimination
PLOS Computational Biology: published July 15, 2015 | https://doi.org/10.1371/journal.pcbi.1004299
Modeling Inhibitory Interneurons in Efficient Sensory Coding Models
PLOS Computational Biology: published July 14, 2015 | https://doi.org/10.1371/journal.pcbi.1004353
A Developmental Switch for Hebbian Plasticity
PLOS Computational Biology: published July 14, 2015 | https://doi.org/10.1371/journal.pcbi.1004386
Geometry of the Gene Expression Space of Individual Cells
PLOS Computational Biology: published July 10, 2015 | https://doi.org/10.1371/journal.pcbi.1004224
Heterogeneous Network Edge Prediction: A Data Integration Approach to Prioritize Disease-Associated Genes
PLOS Computational Biology: published July 9, 2015 | https://doi.org/10.1371/journal.pcbi.1004259
A Computational Model of a Descending Mechanosensory Pathway Involved in Active Tactile Sensing
PLOS Computational Biology: published July 9, 2015 | https://doi.org/10.1371/journal.pcbi.1004263
Evaluating Spatial Interaction Models for Regional Mobility in Sub-Saharan Africa
PLOS Computational Biology: published July 9, 2015 | https://doi.org/10.1371/journal.pcbi.1004267
Genome Modeling System: A Knowledge Management Platform for Genomics
PLOS Computational Biology: published July 9, 2015 | https://doi.org/10.1371/journal.pcbi.1004274
How Co-translational Folding of Multi-domain Protein Is Affected by Elongation Schedule: Molecular Simulations
PLOS Computational Biology: published July 9, 2015 | https://doi.org/10.1371/journal.pcbi.1004356
A Diffusive Homeostatic Signal Maintains Neural Heterogeneity and Responsiveness in Cortical Networks
PLOS Computational Biology: published July 9, 2015 | https://doi.org/10.1371/journal.pcbi.1004389
Stability of Neuronal Networks with Homeostatic Regulation
PLOS Computational Biology: published July 8, 2015 | https://doi.org/10.1371/journal.pcbi.1004357
Predicting Binding Free Energy Change Caused by Point Mutations with Knowledge-Modified MM/PBSA Method
PLOS Computational Biology: published July 6, 2015 | https://doi.org/10.1371/journal.pcbi.1004276
Design of Protein Multi-specificity Using an Independent Sequence Search Reduces the Barrier to Low Energy Sequences
PLOS Computational Biology: published July 6, 2015 | https://doi.org/10.1371/journal.pcbi.1004300
Measuring Asymmetry in Time-Stamped Phylogenies
PLOS Computational Biology: published July 6, 2015 | https://doi.org/10.1371/journal.pcbi.1004312
Thermodynamics and H2 Transfer in a Methanogenic, Syntrophic Community
PLOS Computational Biology: published July 6, 2015 | https://doi.org/10.1371/journal.pcbi.1004364
Structural Model of RNA Polymerase II Elongation Complex with Complete Transcription Bubble Reveals NTP Entry Routes
PLOS Computational Biology: published July 2, 2015 | https://doi.org/10.1371/journal.pcbi.1004354
High Accuracy Decoding of Dynamical Motion from a Large Retinal Population
PLOS Computational Biology: published July 1, 2015 | https://doi.org/10.1371/journal.pcbi.1004304
Rigidity Emerges during Antibody Evolution in Three Distinct Antibody Systems: Evidence from QSFR Analysis of Fab Fragments
PLOS Computational Biology: published July 1, 2015 | https://doi.org/10.1371/journal.pcbi.1004327