Gil Adrià, Carbó Jorge J
ARAID Foundation, Zaragoza, Spain.
Departamento de Química Inorgánica, Instituto de Síntesis Química y Catálisis Homogénea (ISQCH) CSIC, Universidad de Zaragoza, Zaragoza, Spain.
Front Chem. 2022 Apr 14;10:876630. doi: 10.3389/fchem.2022.876630. eCollection 2022.
Polyoxometalates (POMs) structures have raised considerable interest for the last years in their application to biological processes and medicine. Within this area, our mini-review shows that computational modelling is an emerging tool, which can play an important role in understanding the interaction of POMs with biological systems and the mechanisms responsible of their activity, otherwise difficult to achieve experimentally. During recent years, computational studies have mainly focused on the analysis of POM binding to proteins and other systems such as lipid bilayers and nucleic acids, and on the characterization of reaction mechanisms of POMs acting as artificial metalloproteases and phosphoesterases. From early docking studies locating binding sites, molecular dynamics (MD) simulations have allowed to characterize the nature of POM···protein interactions, and to evaluate the effect of the charge, size, and shape of the POM on protein affinity, including also, the atomistic description of chaotropic character of POM anions. Although these studies rely on the interaction with proteins and nucleic acid models, the results could be extrapolated to other biomolecules such as carbohydrates, triglycerides, steroids, terpenes, etc. Combining MD simulations with quantum mechanics/molecular mechanics (QM/MM) methods and DFT calculations on cluster models, computational studies are starting to shed light on the factors governing the activity and selectivity for the hydrolysis of peptide and phosphoester bonds catalysed by POMs.
近年来，多金属氧酸盐（POMs）结构在生物过程和医学应用方面引起了广泛关注。在这一领域，我们的小型综述表明，计算建模是一种新兴工具，在理解POMs与生物系统的相互作用及其活性机制方面可发挥重要作用，否则这些机制很难通过实验实现。近年来，计算研究主要集中在分析POMs与蛋白质以及脂质双层和核酸等其他系统的结合，以及对作为人工金属蛋白酶和磷酸酯酶的POMs反应机制的表征。从早期定位结合位点的对接研究开始，分子动力学（MD）模拟已能够表征POM···蛋白质相互作用的性质，并评估POM的电荷、大小和形状对蛋白质亲和力的影响，其中还包括对POM阴离子离液序列高的原子描述。尽管这些研究依赖于与蛋白质和核酸模型的相互作用，但其结果可以外推到其他生物分子，如碳水化合物、甘油三酯、类固醇、萜类等。将MD模拟与量子力学/分子力学（QM/MM）方法以及对团簇模型的密度泛函理论（DFT）计算相结合，计算研究开始揭示控制POMs催化肽键和磷酸酯键水解活性和选择性的因素。
