ArticleProceedings of the National Academy of Sciences of the United States of America2013
Role of methyl-induced polarization in ion binding.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 45 citations in OpenAlex.
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- Polarizable AMOEBA Model for Simulating MgJournal of chemical information and modeling · 2024Article
- Development of AMOEBA Polarizable Force Field for Rare-Earth LaThe journal of physical chemistry. B · 2023Article
- Effects of glutamine, glutamate, and aspartate on intestinal barrier integrity and amino acid pool of the small intestine in piglets with normal or low energy diet.Frontiers in veterinary science · 2023Article
- Inclusion of High-Field Target Data in AMOEBA's Calibration Improves Predictions of Protein-Ion Interactions.Journal of chemical information and modeling · 2022Article
- Hydrated Anions: From Clusters to Bulk Solution with Quasi-Chemical Theory.Accounts of chemical research · 2022Article
- Methyl-Induced Polarization Destabilizes the Noncovalent Interactions of N-Methylated Lysines.Chemistry (Weinheim an der Bergstrasse, Germany) · 2021Article
- Thermodynamics of ion binding and occupancy in potassium channels.Chemical science · 2021Article
- Pore-forming transmembrane domains control ion selectivity and selectivity filter conformation in the KirBac1.1 potassium channel.The Journal of general physiology · 2021Article
- Predictive QM/MM Modeling of Modulations in Protein-Protein Binding by Lysine Methylation.Journal of molecular biology · 2021Article
- Peptide-Mineral Complexes: Understanding Their Chemical Interactions, Bioavailability, and Potential Application in Mitigating Micronutrient Deficiency.Foods (Basel, Switzerland) · 2020Review
- Transferable interactions of LiThe Journal of chemical physics · 2020Article
- Improved description of ligand polarization enhances transferability of ion-ligand interactions.The Journal of chemical physics · 2020Article
- Ion-Hydroxyl Interactions: From High-Level Quantum Benchmarks to Transferable Polarizable Force Fields.Journal of chemical theory and computation · 2019Article
- Tailoring van der Waals dispersion interactions with external electric charges.Nature communications · 2018Article
- Stimulation of Nipah Fusion: Small Intradomain Changes Trigger Extensive Interdomain Rearrangements.Biophysical journal · 2016Article
- The exceptionally high reactivity of Cys 621 is critical for electrophilic activation of the sensory nerve ion channel TRPA1.The Journal of general physiology · 2016Article
- Cation Selectivity in Biological Cation Channels Using Experimental Structural Information and Statistical Mechanical Simulation.PloS one · 2015Article
- Hydrogen bonds as molecular timers for slow inactivation in voltage-gated potassium channels.eLife · 2013Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The chemical property of methyl groups that renders them indispensable to biomolecules is their hydrophobicity. Quantum mechanical studies undertaken here to understand the effect of point substitutions on potassium (K-) channels illustrate quantitatively how methyl-induced polarization also contributes to biomolecular function. K- channels regulate transmembrane salt concentration gradients by transporting K(+) ions selectively. One of the K(+) binding sites in the channel's selectivity filter, the S4 site, also binds Ba(2+) ions, which blocks K(+) transport. This inhibitory property of Ba(2+) ions has been vital in understanding K-channel mechanism. In most K-channels, the S4 site is composed of four threonine amino acids. The K channels that carry serine instead of threonine are significantly less susceptible to Ba(2+) block and have reduced stabilities. We find that these differences can be explained by the lower polarizability of serine compared with threonine, because serine carries one less branched methyl group than threonine. A T→S substitution in the S4 site reduces its polarizability, which, in turn, reduces ion binding by several kilocalories per mole. Although the loss in binding affinity is high for Ba(2+), the loss in K(+) binding affinity is also significant thermodynamically, which reduces channel stability. These results highlight, in general, how biomolecular function can rely on the polarization induced by methyl groups, especially those that are proximal to charged moieties, including ions, titratable amino acids, sulfates, phosphates, and nucleotides.
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