College of Chemistry & Chemical Engineering, Lanzhou University, Lanzhou 730000, P. R. China.
J Phys Chem B. 2019 Sep 5;123(35):7570-7577. doi: 10.1021/acs.jpcb.9b05147. Epub 2019 Aug 22.
The investigation on proteinlike specific functions of nanoparticles (NPs) has been a huge challenge. Here, the biocompatibility of Au nanoparticles (AuNPs) to antigens hen egg white lysozyme and epidermal growth factor receptor was studied first by molecular dynamics (MD) simulations and the research results revealed that antigens could form quickly a stable binding with the AuNPs and kept the structural integrity of the protein, which demonstrated better biocompatibility of AuNPs. Then, two types of complementary-determining regions (CDRs) were grafted onto the AuNPs to design a novel multi-CDR-functional nanobody. By means of MD simulations under physiological conditions, we found that the bindings of the designed nanobody and the antigens were stable and safe. Compared with the results of antigens interacting with the natural antibody, the redundant CDRs on AuNPs bound with the nonactive site in the antigens to form a stable conformation, which leaded to the powerful binding capacity of the designed nanobody than that of the natural antibody. This study provided available insights into the biocompatibility of AuNPs and important theoretical proofs to the multi-CDR-functional nanobody applied in biological systems, which were expected to help in design of novel multifunctional nanobodies.
研究纳米粒子（NPs）的类蛋白特殊功能一直是一个巨大的挑战。在这里，我们首先通过分子动力学（MD）模拟研究了金纳米粒子（AuNPs）对鸡卵清溶菌酶和表皮生长因子受体抗原的生物相容性，研究结果表明抗原能够与 AuNPs 快速形成稳定的结合，并保持蛋白质的结构完整性，这表明 AuNPs 具有更好的生物相容性。然后，将两种互补决定区（CDRs）接枝到 AuNPs 上，设计了一种新型的多 CDR 功能纳米抗体。通过在生理条件下进行的 MD 模拟，我们发现设计的纳米抗体与抗原的结合是稳定和安全的。与抗原与天然抗体相互作用的结果相比，AuNPs 上的冗余 CDRs 与抗原中的非活性部位结合，形成稳定的构象，这导致设计的纳米抗体比天然抗体具有更强的结合能力。这项研究为 AuNPs 的生物相容性提供了有价值的见解，并为多 CDR 功能纳米抗体在生物系统中的应用提供了重要的理论依据，有望有助于设计新型多功能纳米抗体。
