Format

Send to

Choose Destination
J Mol Graph Model. 2019 Sep;91:194-203. doi: 10.1016/j.jmgm.2019.06.006. Epub 2019 Jun 14.

Activation of human insulin by vitamin E: A molecular dynamics simulation study.

Author information

1
Biophysics Department, Faculty of Biological Sciences, Tarbiat Modares University, 14115-154, Tehran, Iran. Electronic address: hsoleymani@modares.ac.ir.
2
Biophysics Department, Faculty of Biological Sciences, Tarbiat Modares University, 14115-154, Tehran, Iran. Electronic address: mohammad.ghorbani.janatabad@gmail.com.
3
Biophysics Department, Faculty of Biological Sciences, Tarbiat Modares University, 14115-154, Tehran, Iran. Electronic address: a-allahverdi@modares.ac.ir.
4
School of Cognitive Science, Institute for Research in Fundamental Sciences (IPM), 193955746, Tehran, Iran. Electronic address: s.shojaei@ipm.ir.
5
Biophysics Department, Faculty of Biological Sciences, Tarbiat Modares University, 14115-154, Tehran, Iran; School of Biological Science, Institute for Research in Fundamental Sciences (IPM), 19395-5746, Tehran, Iran. Electronic address: naderman@modares.ac.ir.

Abstract

Lack of perfect insulin signaling can lead to the insulin resistance, which is the hallmark of diabetes mellitus. Activation of insulin and its binding to the receptor for signaling process initiates via B-chain C-terminal hinge conformational change through an open structure to "wide-open" conformation. Observational studies and basic scientific evidence suggest that vitamin D and E directly and/or indirectly prevent diabetes through improving glucose secretion and tolerance, activating calcium dependent endopeptidases and thus improving insulin exocytosis, antioxidant effect and reducing insulin resistance. On the contrary, clinical trials have yielded inconsistent results about the efficacy of vitamin D supplementations for the control of glucose hemostasis. In this work, best binding modes of vitamin D3 and E on insulin obtained from AutoDock Vina were selected for Molecular Dynamic, MD, study. The binding energy obtained from Molecular Mechanics- Poisson Boltzman Surface Area, MM-PBSA method, revealed that Vitamins D3 and E have good affinity to bind to the insulin and vitamin E has higher binding energy (-46 kj/mol) by engaging more residues in binding site. Distance and angle calculation results illustrated that vitamin E changes the B-chain conformation and it causes the formation of wide-open/active form of insulin. Vitamin E increases the ValB12-TyrB26 distance to ∼15 Å and changes the hinge angle to ∼65°. Consequently, essential hydrophobic residues for binding to insulin receptor exposed to surface in the presence of vitamin E. However, our data illustrated that vitamin D3 cannot change B-chain conformation. Thus our MD simulations propose a model for insulin activation through vitamin E interaction for therapeutic approaches.

KEYWORDS:

Diabetes mellitus; Hinge opening; Insulin; MM-PBSA; Molecular dynamics simulation

PMID:
31265936
DOI:
10.1016/j.jmgm.2019.06.006

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center