Progress in Simulation Studies of Insulin Structure and Function.
Progress in Simulation Studies of Insulin Structure and Function.
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DOI：
10.3389/fendo.2022.908724
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发表时间：
2022
影响因子：
5.2
通讯作者：
Vashisth H
中科院分区：
文献类型：
--
作者：
Gorai B;Vashisth H
胰岛素是一种肽激素，已知主要用于调节血液中的葡萄糖水平以及其他几种代谢过程。胰岛素仍然是治疗糖尿病最有效的药物。胰岛素在胰腺β-细胞中合成，尽管其生物活性形式是单体，但它以紧凑的六聚体结构存在。胰岛素在从六聚体状态到其生物活性单体状态的转变期间表现出一系列构象变化。胰岛素的结构转变和作用机制已经使用几种实验和计算方法进行了研究。这篇综述主要强调了分子动力学（MD）模拟在阐明胰岛素构象动力学的原子级细节方面的贡献，其中激素的结构已被探测为单体，二聚体和六聚体。在微观尺度上探讨了溶剂、pH值、温度和压力的影响。鉴于这篇综述的重点是激素的结构，涉及激素及其受体之间相互作用的模拟研究仅简要强调，而对其他相关肽的研究（例如，胰岛素样生长因子）。然而，审查强调构象动力学的活动报告的胰岛素类似物和模拟物。计算方法在开发有前途的合成胰岛素类似物的未来前景也简要强调。
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.
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DOI：
10.1073/pnas.88.2.622
发表时间：
1991-01-01
影响因子：
11.1
作者：
BADGER, J;CASPAR, DLD
通讯作者：
CASPAR, DLD
DOI：
10.1098/rstb.1988.0058
发表时间：
1988-07-06
影响因子：
6.3
作者：
BAKER, EN;BLUNDELL, TL;VIJAYAN, NM
通讯作者：
VIJAYAN, NM
影响因子：
3.3
作者：
Bagchi, Kushal;Roy, Susmita
通讯作者：
Roy, Susmita
影响因子：
3.7
作者：
Chiang HL;Ngo ST;Chen CJ;Hu CK;Li MS
通讯作者：
Li MS
影响因子：
4.4
作者：
Banerjee, Puja;Mondal, Sayantan;Bagchi, Biman
通讯作者：
Bagchi, Biman