用于模拟辅助生物传感器设计的带电纳米表面附近的蛋白质取向探测
Probing protein orientation near charged nanosurfaces for simulation-assisted biosensor design
摘要：
蛋白质-表面相互作用在生物过程和生物工程中普遍存在，但尚未完全理解。在生物传感器中，决定灵敏度以及装置性能的关键因素是生物活性装置表面上配体分子的取向。因此，吸附研究试图确定取向如何受到表面制备的影响。在这项工作中，蛋白质的取向附近的带电纳米表面获得静电效应下使用泊松-玻尔兹曼方程，在一个隐式溶剂模型。在相对于带电表面的倾斜角和旋转角的范围内对蛋白质GB 1D 4 '的自由能进行采样，我们计算了蛋白质取向的概率并观察到偶极行为。这一结果与已发表的实验研究和结合蒙特卡罗和分子动力学模拟使用这种小蛋白质，验证我们的方法是一致的。与生物传感器技术更相关的是，抗体（如免疫球蛋白G）仍然是分子模拟的一个巨大挑战，因为它们的尺寸很大。我们得到了在不同的表面电荷和盐浓度的同种型IgG 2a的取向的概率分布。在以前的研究中没有发现这种同种型具有优选的取向，不像同种型IgG 1，其更大的偶极矩被假定为使其更容易控制。我们发现IgG 2a的择优取向在表面正电荷为0.05 C/m $^{2}$或更高和盐浓度为37 mM的情况下有利于生物传感。结果还表明，局部相互作用占主导地位的偶极矩的这种蛋白质。因此，使用我们的方法（和开源代码）的数值研究可以帮助提高免疫测定的灵敏度，指导配体分子的制造方案或蛋白质工程的变化，以获得更有利的方向。
英文摘要：
Protein-surface interactions are ubiquitous in biological processes and bioengineering, yet are not fully understood. In biosensors, a key factor determining the sensitivity and thus the performance of the device is the orientation of the ligand molecules on the bioactive device surface. Adsorption studies thus seek to determine how orientation can be influenced by surface preparation. In this work, protein orientation near charged nanosurfaces is obtained under electrostatic effects using the Poisson-Boltzmann equation, in an implicit-solvent model. Sampling the free energy for protein GB1D4' at a range of tilt and rotation angles with respect to the charged surface, we calculated the probability of the protein orientations and observed a dipolar behavior. This result is consistent with published experimental studies and combined Monte Carlo and molecular dynamics simulations using this small protein, validating our method. More relevant to biosensor technology, antibodies such as immunoglobulin G are still a formidable challenge to molecular simulation, due to their large size. We obtained the probability distribution of orientations for the iso-type IgG2a at varying surface charge and salt concentration. This iso-type was not found to have a preferred orientation in previous studies, unlike the iso-type IgG1 whose larger dipole moment was assumed to make it easier to control. We find that the preferred orientation of IgG2a can be favorable for biosensing with positive surface charge of 0.05C/m$^{2}$ or higher and 37mM salt concentration. The results also show that local interactions dominate over dipole moment for this protein. Improving immunoassay sensitivity may thus be assisted by numerical studies using our method (and open-source code), guiding changes to fabrication protocols or protein engineering of ligand molecules to obtain more favorable orientations.
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