微藻衍生的虾青素调节与2型糖尿病相关的激素受体网络：实验文献支持的计算机研究
Microalgae-derived astaxanthin modulates the hormone receptor network associated with type 2 diabetes mellitus: An in-silico investigation supported by experimental literature.
摘要(中文译文)
微藻虾青素（ASX）在2型糖尿病（T2DM）中的受体层面机制在很大程度上仍不清楚。在本研究中，我们采用系统且整合的计算机模拟工作流程，研究了ASX与胰岛素受体、糖皮质激素受体和胰高血糖素样肽-1（GLP-1）受体模型的受体层面结合兼容性及多靶点相互作用特征，该流程涵盖分子对接、1000 ns分子动力学（MD）模拟、分子力学/泊松-玻尔兹曼表面积（MM/PBSA）结合自由能计算、基于密度泛函理论（DFT）的HOMO-LUMO及分子静电势（MEP）分析，以及吸收、分布、代谢、排泄和毒性（ADMET）分析。结果显示，ASX与T2DM相关靶点受体具有强烈的受体特异性结合特征，其结合能在-8.2至-10.5 kcal/mol范围内。此外，这些结合特征中极性锚定位点和疏水接触的存在支持了对接结果。MD模拟输出还表明，ASX复合物具有高度稳定性，而基于MM/PBSA的结合自由能分别为胰高血糖素样肽-1受体（GLP-1R）-45.86 kcal/mol、糖皮质激素受体-45.08 kcal/mol和胰岛素受体（INSR）-34.12 kcal/mol，定量支持了这一稳定性。我们的DFT分析结果还揭示了ASX具有较低的HOMO-LUMO能隙、离域的前线分子轨道分布以及自适应静电特性，证明了该微藻配体在靶点受体微环境中的电子兼容性。ASX的ADMET研究结果表明，尽管其肠道通透性有限，但在心脏安全性和CYP抑制方面具有良好的药代动力学特性。在此背景下，基于其构象稳定化、热力学兼容性和电子适应特征，微藻ASX可能成为胰岛素-胰高血糖素-GLP-1轴内一种受体兼容的多靶点候选物。
Abstract
Receptor-level mechanisms of microalgal astaxanthin (ASX) in T2DM remain largely unknown. In our study, the receptor-level binding compatibility and multi-target interaction profile of ASX with insulin, glucocorticoid, and glucagon-like peptide-1 (GLP-1) receptor models were investigated using a systematic and integrated in-silico workflow encompassing molecular docking, 1000 ns molecular dynamics (MD) simulations, molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA) binding free energy calculations, density functional theory (DFT)-based HOMO-LUMO and molecular electrostatic potential (MEP) analyses, and absorption, distribution, metabolism, excretion, and toxicity (ADMET) analyses. Strong receptor-specific binding profiles were revealed for the target receptors associated with T2DM, with ASX binding energies ranging from -8.2 to -10.5 kcal/mol. Additionally, the presence of polar anchoring sites and hydrophobic contacts in these profiles supports the docking findings. MD simulation outputs also revealed that the ASX complexes were highly stable, while the MM/PBSA-based binding free energies of -45.86, -45.08, and -34.12 kcal/mol for glucagon-like peptide-1 receptor (GLP-1R), the glucocorticoid receptor, and insulin receptor (INSR), respectively, quantitatively supported this stability. Our DFT analysis findings also revealed ASX's low HOMO-LUMO energy gap, delocalized frontier molecular orbital distributions, and adaptive electrostatic properties, demonstrating the electronic compatibility of this microalgal ligand in the target receptor microenvironments. The ADMET findings of ASX revealed that, despite its limited intestinal permeability, it possesses favorable pharmacokinetic properties in terms of cardiac safety and CYP inhibition. In this context, microalgal ASX may represent a receptor-compatible multi-target candidate within the insulin-glucagon-GLP-1 axis, based on its conformational stabilization, thermodynamic compatibility, and electronic adaptation profiles.
如何引用
AMA
Nil Sazlı, Deniz Karataş. Microalgae-derived astaxanthin modulates the hormone receptor network associated with type 2 diabetes mellitus: An in-silico investigation supported by experimental literature.. Computational biology and chemistry. 2026; doi:10.1016/j.compbiolchem.2026.109146.
APA
Nil Sazlı, Deniz Karataş (2026). Microalgae-derived astaxanthin modulates the hormone receptor network associated with type 2 diabetes mellitus: An in-silico investigation supported by experimental literature.. Computational biology and chemistry. https://doi.org/10.1016/j.compbiolchem.2026.109146
GB/T 7714
Nil Sazlı, Deniz Karataş. Microalgae-derived astaxanthin modulates the hormone receptor network associated with type 2 diabetes mellitus: An in-silico investigation supported by experimental literature.[J]. Computational biology and chemistry, 2026 doi:10.1016/j.compbiolchem.2026.109146.
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