Dipartimento di Scienze Chimiche, Univeristà di Padova, Via Marzolo 1, 35131, Padova, Italy.
Laboratory of Molecular Modeling & Drug Discovery, Istituto Italiano di Tecnologia (IIT), Via Morego 30, 16163, Genova, Italy.
Angew Chem Int Ed Engl. 2019 Jun 3;58(23):7702-7707. doi: 10.1002/anie.201902316. Epub 2019 May 2.
Here, we demonstrate the possibility of rationally designing nanoparticle receptors with targeted affinity and selectivity for specific small molecules. We used atomistic molecular-dynamics (MD) simulations to gradually mutate and optimize the chemical structure of the molecules forming the coating monolayer of gold nanoparticles (1.7 nm gold-core size). The MD-directed design resulted in nanoreceptors with a 10-fold improvement in affinity for the target analyte (salicylate) and a 100-fold decrease of the detection limit by NMR-chemosensing from the millimolar to the micromolar range. We could define the exact binding mode, which features prolonged contacts and deep penetration of the guest into the monolayer, as well as a distinct shape of the effective binding pockets characterized by exposed interacting points.
在这里，我们展示了合理设计具有针对特定小分子的靶向亲和力和选择性的纳米颗粒受体的可能性。我们使用原子分子动力学 (MD) 模拟来逐步突变和优化形成金纳米粒子 (1.7nm 金核尺寸) 涂层单层的分子的化学结构。MD 导向设计导致纳米受体对目标分析物 (水杨酸酯) 的亲和力提高了 10 倍，通过 NMR 化学感应检测限从毫摩尔降低到微摩尔范围降低了 100 倍。我们可以定义确切的结合模式，其特征是客体与单层的长时间接触和深入渗透，以及具有暴露的相互作用点的有效结合口袋的独特形状。
