Progress in Simulation Studies of Insulin Structure and Function.
computer simulation
diabetes
hormone
insulin
insulin receptor
molecular dynamics
peptide
Journal
Frontiers in endocrinology
ISSN: 1664-2392
Titre abrégé: Front Endocrinol (Lausanne)
Pays: Switzerland
ID NLM: 101555782
Informations de publication
Date de publication:
2022
2022
Historique:
received:
30
03
2022
accepted:
28
04
2022
entrez:
7
7
2022
pubmed:
8
7
2022
medline:
9
7
2022
Statut:
epublish
Résumé
Insulin is a peptide hormone known for chiefly regulating glucose level in blood among several other metabolic processes. Insulin remains the most effective drug for treating diabetes mellitus. Insulin is synthesized in the pancreatic β-cells where it exists in a compact hexameric architecture although its biologically active form is monomeric. Insulin exhibits a sequence of conformational variations during the transition from the hexamer state to its biologically-active monomer state. The structural transitions and the mechanism of action of insulin have been investigated using several experimental and computational methods. This review primarily highlights the contributions of molecular dynamics (MD) simulations in elucidating the atomic-level details of conformational dynamics in insulin, where the structure of the hormone has been probed as a monomer, dimer, and hexamer. The effect of solvent, pH, temperature, and pressure have been probed at the microscopic scale. Given the focus of this review on the structure of the hormone, simulation studies involving interactions between the hormone and its receptor are only briefly highlighted, and studies on other related peptides (e.g., insulin-like growth factors) are not discussed. However, the review highlights conformational dynamics underlying the activities of reported insulin analogs and mimetics. The future prospects for computational methods in developing promising synthetic insulin analogs are also briefly highlighted.
Identifiants
pubmed: 35795141
doi: 10.3389/fendo.2022.908724
pmc: PMC9252437
doi:
Substances chimiques
Insulin
0
Types de publication
Journal Article
Review
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
908724Subventions
Organisme : NIGMS NIH HHS
ID : R35 GM138217
Pays : United States
Informations de copyright
Copyright © 2022 Gorai and Vashisth.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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