Predicting protein function and orientation on a gold nanoparticle surface using a residue-based affinity scale.
Predicting protein function and orientation on a gold nanoparticle surface using a residue-based affinity scale.
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DOI：
10.1038/s41467-022-34749-w
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发表时间：
2022-11-27
影响因子：
16.6
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中科院分区：
文献类型：
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作者：
蛋白质在纳米颗粒表面的取向决定了纳米颗粒的生物活性及其与生命系统的相互作用。在这里，我们提出了一个基于残基的亲和力尺度预测柠檬酸金纳米粒子（AuNPs）上的蛋白质取向。蛋白质变体之间的竞争性结合解释了该尺度下吸附的热力学和动力学方面。对于疏水性残基，空间的考虑占主导地位，而静电相互作用是关键的亲水性残基。该规模合理化的小GB3蛋白的明确定义的结合方向，并随后预测的方向和活性位点的两种酶对金纳米粒子的访问。此外，我们的方法考虑了文献中六种额外酶中五种的AuNP结合活性。这里开发的模型能够高通量预测纳米颗粒上的蛋白质行为，它增强了我们对生物分子冠中蛋白质取向的理解，这将大大提高体内使用的纳米药物的性能和安全性。蛋白质在纳米颗粒表面上的取向对于纳米颗粒在体内的命运是重要的。在这里，作者利用蛋白质变体之间的竞争性结合来开发基于残基的亲和力尺度，从而开发出蛋白质在金纳米颗粒上的结合和取向的模型
The orientation adopted by proteins on nanoparticle surfaces determines the nanoparticle’s bioactivity and its interactions with living systems. Here, we present a residue-based affinity scale for predicting protein orientation on citrate-gold nanoparticles (AuNPs). Competitive binding between protein variants accounts for thermodynamic and kinetic aspects of adsorption in this scale. For hydrophobic residues, the steric considerations dominate, whereas electrostatic interactions are critical for hydrophilic residues. The scale rationalizes the well-defined binding orientation of the small GB3 protein, and it subsequently predicts the orientation and active site accessibility of two enzymes on AuNPs. Additionally, our approach accounts for the AuNP-bound activity of five out of six additional enzymes from the literature. The model developed here enables high-throughput predictions of protein behavior on nanoparticles, and it enhances our understanding of protein orientation in the biomolecular corona, which should greatly enhance the performance and safety of nanomedicines used in vivo. The orientation of proteins on nanoparticle surfaces is important to the nanoparticle’s fate in vivo. Here, the authors use competitive binding between protein variants to develop a residue-based affinity scale to develop a model for the binding and orientation of proteins on gold nanoparticles