University for Applied Sciences of Southern Switzerland (SUPSI)-Institute of Computer Integrated Manufacturing for Sustainable Innovation, Centro Galleria 2, Manno, CH-6928, Switzerland.
J Phys Chem B. 2010 Mar 4;114(8):2667-75. doi: 10.1021/jp100271w.
This paper reports a molecular dynamic study to explore the diverse behavior of different generations of poly(amidoamine) (PAMAM) dendrimers in binding siRNA. Our models show good accordance with experimental measurements. Simulations demonstrate that the molecular flexibility of PAMAMs plays a crucial role in the binding event, which is controlled by the modulation between enthalpy and entropy of binding. Importantly, the ability of dendrimers to adapt to siRNA is strongly dependent on the generation and on the pH due to backfolding. While G4 demonstrates good adaptability to siRNA, G6 behaves like a rigid sphere with a consistent loss in the binding affinity. G5 shows a hybrid behavior, maintaining rigid and flexible aspects, with a strong dependence of its properties on the pH. To define the "best binder", the mere energetic definition of binding affinity appears to be no longer effective and a novel concept of "efficiency" should be considered, being the balance between enthalpy and entropy of binding indivisible from the structural flexibility. With this aim, we propose an original criterion to define and rank the ability of these molecules to adapt their structure to bind a charged target.
本文报道了一项分子动力学研究，旨在探索不同代数的聚（酰胺-胺）（PAMAM）树枝状大分子与 siRNA 结合的不同行为。我们的模型与实验测量结果吻合良好。模拟表明，PAMAMs 的分子柔性在结合事件中起着关键作用，这是由结合焓和熵之间的调制控制的。重要的是，由于回折，树枝状大分子与 siRNA 适应的能力强烈依赖于代数和 pH。虽然 G4 对 siRNA 具有良好的适应性，但 G6 表现得像一个刚性球体，结合亲和力持续下降。G5 表现出混合行为，保持刚性和柔性方面，其性质强烈依赖于 pH。为了定义“最佳结合物”，仅仅基于结合亲和力的能量定义似乎不再有效，应该考虑一个新的“效率”概念，即结合焓和熵之间的平衡与结构柔性不可分割。为此，我们提出了一个原始标准来定义和排序这些分子适应其结构以结合带电荷靶标的能力。
