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 Au₁₀₂pMBA₄₄ 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.

中文翻译：

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通过非平衡分子动力学模拟探索用金纳米团簇标记病毒的策略

生物相容性金纳米簇可用作病毒成像中的造影剂。可以通过类脂脂质因子将簇连接到病毒的疏水性口袋上，从而非共价地但特异性地实现病毒的标记。我们已经在结合非平衡自由能计算的分子动力学模拟中估计了回声病毒1（EV1）的三个不同口袋因子的结合亲和力。我们还研究了与Au ₁₀₂ p MBA ₄₄相关的口袋因子对结合亲和力的影响。不同质子化状态的纳米簇。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。3我们的结果表明，天然口袋因子（棕榈酸）可以被pleconaril（药物）及其衍生物Kirtan1代替。具有更高的估计结合亲和力。我们的结果还表明，包括金纳米团簇并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。这项工作中介绍的方法学有助于设计用于病毒检测和处理的金病毒生物缀合的最佳策略。