ArticleProceedings of the National Academy of Sciences of the United States of America2007
On the thermodynamic stability of a charged arginine side chain in a transmembrane helix.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 137 papers.
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137 citing papers in PubMed, 264 citations in OpenAlex.
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- Thermodynamics of arginine interactions with organic phosphates.Biophysical journal · 2025Article
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- Vastly different energy landscapes of the membrane insertions of monomeric gasdermin D and A3.Communications chemistry · 2025Article
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- Free Energy Profile Decomposition Analysis for QM/MM Simulations of Enzymatic Reactions.Journal of chemical theory and computation · 2023Article
- A multiscale predictive digital twin for neurocardiac modulation.The Journal of physiology · 2023Article
- Recent Advances of Studies on Cell-Penetrating Peptides Based on Molecular Dynamics Simulations.Cells · 2022Review
- Amphiphilic Gold Nanoparticles: A Biomimetic Tool to Gain Mechanistic Insights into Peptide-Lipid Interactions.Membranes · 2022Review
- Ataxia-linked SLC1A3 mutations alter EAAT1 chloride channel activity and glial regulation of CNS function.The Journal of clinical investigation · 2022Article
- Differential Pathomechanisms of Desmoglein 1 Transmembrane Domain Mutations in Skin Disease.The Journal of investigative dermatology · 2022Article
- Not sorcery after all: Roles of multiple charged residues in membrane insertion of gasdermin-A3.Frontiers in cell and developmental biology · 2022Article
- Free Energy Analyses of Cell-Penetrating Peptides Using the Weighted Ensemble Method.Membranes · 2021Article
- Vectorial insertion of a β-helical peptide into membrane: a theoretical study on polytheonamide B.Biophysical journal · 2021Article
- Thermodynamics and Mechanism of the Membrane Permeation of Hv1 Channel Blockers.The Journal of membrane biology · 2021Article
- Characterizing Hydropathy of Amino Acid Side Chain in a Protein Environment by Investigating the Structural Changes of Water Molecules Network.Frontiers in molecular biosciences · 2021Article
77 more citing papers are in PubMed but not listed here.
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Biological membranes consist of bilayer arrangements of lipids forming a hydrophobic core that presents a physical barrier to all polar and charged molecules. This long-held notion has recently been challenged by biological translocon-based experiments that report small apparent free energies to insert charged side chains near the center of a transmembrane (TM) helix. We have carried out fully atomistic simulations to provide the free-energy profile for moving a TM helix containing a protonated Arg side chain across a lipid bilayer. Our results reveal the fundamental thermodynamics governing the stability of charged side chains in membranes and the microscopic interactions involved. Despite local membrane deformations, where large amounts of water and lipid head groups are pulled into the bilayer to interact with Arg, the free-energy barrier is 17 kcal/mol. We provide a rationale for the differences in our microscopic free energies and cell biological experiments using free-energy calculations that indicate that a protonated Arg at the central residue of a TM helix of the Leader peptidase might reside close to the interface and not at the membrane center. Our findings have implications for the gating mechanisms of voltage-gated ion channels, suggesting that movements of protonated Arg residues through the membrane will be prohibited.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.