In the applications molecular machines, the function of the nanostructures depends exquisitely upon the motion at play. Movements of their components observed in molecular machines are usually diverse and complex. Case in point, shuttling, rotation and isomerization, which are commonly viewed as independent motions, when, in reality, they are often coupled. Exploring the multidimensional free-energy surface of these complex processes is often hampered by significant free-energy barriers corresponding to the entangled movements. Therefore, a complete decryption at the atomic level of these motions still remains challenging. Here, we report an adaptive biasing force (ABF)-based importance sampling algorithm, on-the-flying extended ABF (eABF), and its new variant meta-eABF, and two applications of these methods in rotaxane-based molecular machines. (1) It has been reported that water can significantly accelerate the relative motion of the components in hydrogen-bonded rotaxanes. Why does water alone possess this unique property? To answer this question, we have investigated a prototypical hydrogen-bonded rotaxane in four different solvents. The two-dimensional free-energy landscape that characterizes the coupled shuttling and conformational change of the macrocycle is mapped employing the eABF algorithm. Our results indicate that water lubricates the shuttling of rotaxanes by altering the mechanism underlying the movements of translation coupled with conformational change of the macrocycle. Moreover, we found that the high polarity, the hydrogen-bond donor and acceptor ability, and the minimal steric hindrance of water are responsible for the lubrication by water. (2) We have examined at the atomic level a prototypical pH-responsive molecular shuttle-based optical switch using the meta-eABF algorithm. The coupled shuttling, rotation and isomerization of the macrocycle are explored at low and high pH with the aid of three-dimensional free-energy calculations. Our results demonstrate that static crystal structures alone are insufficient to reveal the full mechanism of fluorescence regulation. π-stacking interactions in both the crystallographic structure and the metastable state of the optical switch induce quenching. In addition, the inherent relationship between optical properties and macrocycle isomerization revealed herein indicates that fluorescence can be used as a probe to sense the dynamic conformational changes of rotaxanes in motion.

Decryption of the diverse and complex movements in molecular machines

2019 Fall National Meeting

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