ArticlePloS one2015
Molecular Dynamics Simulations of Insulin: Elucidating the Conformational Changes that Enable Its Binding.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 29 citations in OpenAlex.
- Dual Mechanistic Role of Polyphenols in Modulating the Insulin-Related Metabolic Pathways: Insights from Computer-Aided Analysis.Cell biochemistry and biophysics · 2026Article
- Effects of acetylation on human insulin structure, and dynamics at different temperatures: A molecular dynamics simulation study.Journal of biosciences · 2026Article
- Stabilization of a protein by a single halogen-based aromatic amplifier.Protein science : a publication of the Protein Society · 2025Article
- Exploring proinsulin proteostasis: insights into beta cell health and diabetes.Frontiers in molecular biosciences · 2025Review
- Computational Approach to Elucidating Insulin-Protamine Binding Interactions and Dynamics in Insulin NPH Formulations.ACS omega · 2024Article
- The TActa crystallographica. Section D, Structural biology · 2023Article
- Understanding Insulin in the Age of Precision Medicine and Big Data: Under-Explored Nature of Genomics.Biomolecules · 2023Review
- Single-chain insulin analogs threaded by the insulin receptor αCT domain.Biophysical journal · 2022Article
- Progress in Simulation Studies of Insulin Structure and Function.Frontiers in endocrinology · 2022Review
- Mutations at hypothetical binding site 2 in insulin and insulin-like growth factors 1 and 2 result in receptor- and hormone-specific responses.The Journal of biological chemistry · 2019Article
- Probing the correlation between insulin activity and structural stability through introduction of the rigid A6-A11 bond.The Journal of biological chemistry · 2018Article
- Human long intrinsically disordered protein regions are frequent targets of positive selection.Genome research · 2018Article
- Computational study of the activity, dynamics, energetics and conformations of insulin analogues using molecular dynamics simulations: Application to hyperinsulinemia and the critical residue B26.Biochemistry and biophysics reports · 2017Article
- Equilibrium Ensembles for Insulin Folding from Bias-Exchange Metadynamics.Biophysical journal · 2017Article
- Extending Halogen-based Medicinal Chemistry to Proteins: IODO-INSULIN AS A CASE STUDY.The Journal of biological chemistry · 2016Article
- Contribution of TyrB26 to the Function and Stability of Insulin: STRUCTURE-ACTIVITY RELATIONSHIPS AT A CONSERVED HORMONE-RECEPTOR INTERFACE.The Journal of biological chemistry · 2016Article
- Elucidating the Activation Mechanism of the Insulin-Family Proteins with Molecular Dynamics Simulations.PloS one · 2016Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A sequence of complex conformational changes is required for insulin to bind to the insulin receptor. Recent experimental evidence points to the B chain C-terminal (BC-CT) as the location of these changes in insulin. Here, we present molecular dynamics simulations of insulin that reveal new insights into the structural changes occurring in the BC-CT. We find three key results: 1) The opening of the BC-CT is inherently stochastic and progresses through an open and then a "wide-open" conformation--the wide-open conformation is essential for receptor binding, but occurs only rarely. 2) The BC-CT opens with a zipper-like mechanism, with a hinge at the Phe24 residue, and is maintained in the dominant closed/inactive state by hydrophobic interactions of the neighboring Tyr26, the critical residue where opening of the BC-CT (activation of insulin) is initiated. 3) The mutation Y26N is a potential candidate as a therapeutic insulin analogue. Overall, our results suggest that the binding of insulin to its receptor is a highly dynamic and stochastic process, where initial docking occurs in an open conformation and full binding is facilitated through interactions of insulin receptor residues with insulin in its wide-open conformation.
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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.