ArticleSoft matter2024
Deciphering the influence of Y12L and N17H substitutions on the conformation and oligomerization of human calcitonin.
Article in Soft matter, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
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The trial behind it
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Who cites it
8 citing papers in PubMed, 10 citations in OpenAlex.
- Molecular-level understanding of the aging bone and regeneration mechanisms using computational methods.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2026Review
- Conformational Ensemble Dynamics of Intrinsically Disordered Full-Length α- and β-Synuclein Monomers.Journal of chemical information and modeling · 2025Article
- The Glycine-Rich Region as a Flexible Molecular Glue Promoting hPrPJournal of chemical information and modeling · 2025Article
- Computational exploration of the self-aggregation mechanisms of phenol-soluble modulins β1 and β2 in Staphylococcus aureus biofilms.Colloids and surfaces. B, Biointerfaces · 2025Article
- Computational insights into the aggregation mechanism of human calcitonin.International journal of biological macromolecules · 2025Article
- Computational insights into the aggregation mechanism and amyloidogenic core of aortic amyloid medin polypeptide.Colloids and surfaces. B, Biointerfaces · 2024Article
- Computational Investigation of Coaggregation and Cross-Seeding between Aβ and hIAPP Underpinning the Cross-Talk in Alzheimer's Disease and Type 2 Diabetes.Journal of chemical information and modeling · 2024Article
- Molecular Insights into the Effects of F16L and F19L Substitutions on the Conformation and Aggregation Dynamics of Human Calcitonin.Journal of chemical information and modeling · 2024Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
The abnormal aggregation of human calcitonin (hCT) hormone peptides impairs their physiological function, leading to harmful immune responses and cytotoxicity, which limits their clinical utility. Interestingly, a representative hCT analog incorporating Y12L and N17H substitutions (DM-hCT) has shown reduced aggregation tendencies while maintaining bioactivity. But the molecular mechanism of Y12L and N17H substitutions on the conformational dynamics of hCT remains unclear. Here, we systematically investigated the folding and self-assembly dynamics of hCT and DM-hCT using atomistic discrete molecular dynamics (DMD) simulations. Our findings revealed that hCT monomers predominantly adopted unstructured conformations with dynamic helices. Oligomerization of hCT resulted in the formation of β-sheet-rich aggregates and β-barrel intermediates. The Y12L and N17H substitutions enhanced helical conformations and suppressed β-sheet formation in both monomers and oligomers. These substitutions stabilized the dynamic helices and disrupted aromatic interactions responsible for β-sheet formation at residue 12. Notably, DM-hCT assemblies still exhibited β-sheets in phenylalanine-rich and C-terminal hydrophobic regions, suggesting that future optimizations should focus on these areas. Our simulations provide insights into the molecular mechanisms underlying hCT aggregation and the amyloid-resistant effects of Y12L and N17H substitutions. These findings have valuable implications for the development of clinical hCT analogs.
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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.