Force and Stress along Simulated Dissociation Pathways of Cucurbituril-Guest Systems.
Force and Stress along Simulated Dissociation Pathways of Cucurbituril-Guest Systems.
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DOI：
10.1021/ct2006902
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发表时间：
2012-03-13
影响因子：
5.5
通讯作者：
Gilson, Michael K.
中科院分区：
文献类型：
--
作者：
Velez-Vega, Camilo;Gilson, Michael K.
主客体化学领域为生物分子识别提供了计算上易于处理且信息丰富的模型系统。我们应用分子动力学模拟来研究与具有高结合亲和力的水性葫芦脲-客体复合物的强制解离相关的力和机械应力。首先，使用等速拉力（转向动力学）和软弹簧常数对解绑转变进行建模，以模拟原子力显微镜 (AFM) 实验。计算出的长度力分布产生的断裂力与现有测量值非常一致。我们还使用具有高弹簧常数的转向动力学来生成以严格控制指定拉动距离为特征的路径；然后通过伞式采样模拟平衡这些路径，并用于计算沿解离路径的时间平均机械应力。事实证明，应力计算可以提供有关决定长度力分布和断裂力的关键相互作用的信息。特别是，我们发现一种复合物的非结合转变是一个逐步的过程，最初由客体的铵和主体的羰基之间的静电相互作用主导，随后受到客体庞大的双环辛烷部分的萃取的限制；后一步需要在葫芦脲的提取入口处进行一些键拉伸。相反，第二个复合物与更细长的客体的解离主要是由不同客体的铵和主体的羰基之间的连续静电相互作用驱动的。这些计算还提供了有关这些强制解离过程中热力学不可逆性起源的信息。
The field of host-guest chemistry provides computationally tractable yet informative model systems for biomolecular recognition. We applied molecular dynamics simulations to study the forces and mechanical stresses associated with forced dissociation of aqueous cucurbituril-guest complexes with high binding affinities. First, the unbinding transitions were modeled with constant velocity pulling (steered dynamics) and a soft spring constant, to model atomic force microscopy (AFM) experiments. The computed length-force profiles yield rupture forces in good agreement with available measurements. We also used steered dynamics with high spring constants to generate paths characterized by a tight control over the specified pulling distance; these paths were then equilibrated via umbrella sampling simulations and used to compute time-averaged mechanical stresses along the dissociation pathways. The stress calculations proved to be informative regarding the key interactions determining the length-force profiles and rupture forces. In particular, the unbinding transition of one complex is found to be a stepwise process, which is initially dominated by electrostatic interactions between the guest’s ammoniums and the host’s carbonyl groups, and subsequently limited by the extraction of the guest’s bulky bicyclooctane moiety; the latter step requires some bond stretching at the cucurbituril’s extraction portal. Conversely, the dissociation of a second complex with a more slender guest is mainly driven by successive electrostatic interactions between the different guest’s ammoniums and the host’s carbonyl groups. The calculations also provide information on the origins of thermodynamic irreversibilities in these forced dissociation processes.
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影响因子：
5.5
作者：
Hess, Berk;Kutzner, Carsten;Lindahl, Erik
通讯作者：
Lindahl, Erik
影响因子：
15
作者：
Colizzi, Francesco;Perozzo, Remo;Cavalli, Andrea
通讯作者：
Cavalli, Andrea
影响因子：
56.9
作者：
Grubmuller, H;Heymann, B;Tavan, P
通讯作者：
Tavan, P
影响因子：
4.4
作者：
HARDY, RJ
通讯作者：
HARDY, RJ
DOI：
10.1039/ft9949001507
发表时间：
1994-06-07
期刊：
JOURNAL OF THE CHEMICAL SOCIETY-FARADAY TRANSACTIONS
影响因子：
--
作者：
HOFFMANN, R;KNOCHE, W;BUSCHMANN, HJ
通讯作者：
BUSCHMANN, HJ