Paper Citing NAMD - Abstract
Liu, Peng; Chipot, Christophe; Shao, Xueguang; Cai, Wensheng
Solvent-Controlled Shuttling in a Molecular Switch
JOURNAL OF PHYSICAL CHEMISTRY C, 116:4471-4476, FEB 23 2012
Rotaxanes driven by solvents have been shown to facilitate translocation of drugs into cells. Shuttling is critical to fulfill this function. Despite the importance of this solvent-driven motion, the mechanism that underlies shuttling remains unclear. In the present contribution, a molecular shuttle controlled by solvent, and formed of alpha-cyclodextrin (alpha-CD), dodecamethylene, and bipyridinium moieties, has been studied by means of microsecond time scale molecular dynamics simulations combined with free-energy calculations. Shuttling driven by both solvent and temperature has been investigated by determining the potentials of mean force (PMF) that delineate the process of moving the alpha-CD along the thread in DMSO and water, at 300 and 400 K. In DMSO, the barriers of the PMFs at both temperatures appear to be virtually the same. At low temperature, however, site exchange of the CD is slowed down. In contrast, the barrier in water is shown to be 4.0 kcal/mol higher than in DMSO, thwarting site exchange. Partitioning the PMFs into free-energy components suggests, in contrast with DMSO, that water interacts favorably with the bipyridium moieties, but less so with the alkyl chain, hence yielding a higher free-energy barrier. This observation is supported by the analysis of the structural features of the rotaxanes from the molecular dynamics trajectories.
