ArticleThe journal of physical chemistry. B2020
Insulin Dissociates by Diverse Mechanisms of Coupled Unfolding and Unbinding.
Article in The journal of physical chemistry. B, 2020. 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.
- Multidimensional Infrared Spectroscopy as a Bioanalytical Technique.Chemical reviews · 2026Review
- Analysis of the Dynamics of a Complex, Multipathway Reaction: Insulin Dimer Dissociation.The journal of physical chemistry. B · 2024Article
- Ligand Gaussian Accelerated Molecular Dynamics 3 (LiGaMD3): Improved Calculations of Binding Thermodynamics and Kinetics of Both Small Molecules and Flexible Peptides.Journal of chemical theory and computation · 2024Article
- Ligand Gaussian accelerated Molecular Dynamics 3 (LiGaMD3): Improved Calculations of Binding Thermodynamics and Kinetics of Both Small Molecules and Flexible Peptides.bioRxiv : the preprint server for biology · 2024Article
- Exploring Kinase Asp-Phe-Gly (DFG) Loop Conformational Stability with AlphaFold2-RAVE.Journal of chemical information and modeling · 2024Article
- Using 2D-IR Spectroscopy to Measure the Structure, Dynamics, and Intermolecular Interactions of Proteins in HAccounts of chemical research · 2024Review
- Article
- Understanding the sources of error in MBAR through asymptotic analysis.The Journal of chemical physics · 2023Article
- Predicting Biomolecular Binding Kinetics: A Review.Journal of chemical theory and computation · 2023Review
- Ligand Gaussian Accelerated Molecular Dynamics 2 (LiGaMD2): Improved Calculations of Ligand Binding Thermodynamics and Kinetics with Closed Protein Pocket.Journal of chemical theory and computation · 2023Article
- Identifying signatures of proteolytic stability and monomeric propensity in O-glycosylated insulin using molecular simulation.Journal of computer-aided molecular design · 2022Article
- Protein-Protein Interaction-Gaussian Accelerated Molecular Dynamics (PPI-GaMD): Characterization of Protein Binding Thermodynamics and Kinetics.Journal of chemical theory and computation · 2022Article
- Current State and Principles of Basal Insulin Therapy in Type 2 Diabetes.Journal of clinical medicine research · 2022Review
- Progress in Simulation Studies of Insulin Structure and Function.Frontiers in endocrinology · 2022Review
- Challenges and frontiers of computational modelling of biomolecular recognition.QRB discovery · 2022Article
- Resolving Dynamics in the Ensemble: Finding Paths through Intermediate States and Disordered Protein Structures.The journal of physical chemistry. B · 2021Article
- Kinetics of Phenol Escape from the Insulin RThe journal of physical chemistry. B · 2021Article
- Structural Ensemble of the Insulin Monomer.Biochemistry · 2021Article
- Computational IR Spectroscopy of Insulin Dimer Structure and Conformational Heterogeneity.The journal of physical chemistry. B · 2021Article
- Long-Time-Scale Predictions from Short-Trajectory Data: A Benchmark Analysis of the Trp-Cage Miniprotein.Journal of chemical theory and computation · 2021Article
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Authors and funding
8 authors.
Funding
Abstract
The protein hormone insulin exists in various oligomeric forms, and a key step in binding its cellular receptor is dissociation of the dimer. This dissociation process and its corresponding association process have come to serve as paradigms of coupled (un)folding and (un)binding more generally. Despite its fundamental and practical importance, the mechanism of insulin dimer dissociation remains poorly understood. Here, we use molecular dynamics simulations, leveraging recent developments in umbrella sampling, to characterize the energetic and structural features of dissociation in unprecedented detail. We find that the dissociation is inherently multipathway with limiting behaviors corresponding to conformational selection and induced fit, the two prototypical mechanisms of coupled folding and binding. Along one limiting path, the dissociation leads to detachment of the C-terminal segment of the insulin B chain from the protein core, a feature believed to be essential for receptor binding. We simulate IR spectroscopy experiments to aid in interpreting current experiments and identify sites where isotopic labeling can be most effective for distinguishing the contributions of the limiting mechanisms.
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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.