Pohjolainen Emmi, Malola Sami, Groenhof Gerrit, Häkkinen Hannu
Department of Physics and ‡Department of Chemistry, Nanoscience Center, University of Jyväskylä , Jyväskylä, Finland FI-40014.
Bioconjug Chem. 2017 Sep 20;28(9):2327-2339. doi: 10.1021/acs.bioconjchem.7b00367. Epub 2017 Aug 29.
Biocompatible gold nanoclusters can be utilized as contrast agents in virus imaging. The labeling of viruses can be achieved noncovalently but site-specifically by linking the cluster to the hydrophobic pocket of a virus via a lipid-like pocket factor. We have estimated the binding affinities of three different pocket factors of echovirus 1 (EV1) in molecular dynamics simulations combined with non-equilibrium free-energy calculations. We have also studied the effects on binding affinities with a pocket factor linked to the AupMBA nanocluster in different protonation states. Although the absolute binding affinities are over-estimated for all the systems, the trend is in agreement with recent experiments.3 Our results suggest that the natural pocket factor (palmitic acid) can be replaced by molecules pleconaril (drug) and its derivative Kirtan1 that have higher estimated binding affinities. Our results also suggest that including the gold nanocluster does not decrease the affinity of the pocket factor to the virus, but the affinity is sensitive to the protonation state of the nanocluster, i.e., to pH conditions. The methodology introduced in this work helps in the design of optimal strategies for gold-virus bioconjugation for virus detection and manipulation.
生物相容性金纳米团簇可作为病毒成像的造影剂。通过一种类脂口袋因子将团簇连接到病毒的疏水口袋上，可实现病毒的非共价但位点特异性标记。我们在分子动力学模拟结合非平衡自由能计算中估计了1型艾柯病毒（EV1）三种不同口袋因子的结合亲和力。我们还研究了与处于不同质子化状态的AupMBA纳米团簇相连的口袋因子对结合亲和力的影响。尽管所有系统的绝对结合亲和力都被高估了，但趋势与最近的实验一致。我们的结果表明，天然口袋因子（棕榈酸）可以被具有更高估计结合亲和力的药物普来可那立及其衍生物Kirtan1所取代。我们的结果还表明，包含金纳米团簇不会降低口袋因子对病毒的亲和力，但亲和力对纳米团簇的质子化状态敏感，即对pH条件敏感。这项工作中引入的方法有助于设计用于病毒检测和操控的金-病毒生物共轭的最佳策略。
