Paper Citing NAMD - Abstract
Guo, Tao; Li, Haiyan; Wu, Li; Guo, Zhen; Yin, Xianzhen; Wang, Caifen; Sun, Lixin; Shao, Qun; Gu, Jingkai; York, Peter; Zhang, Jiwen
Prediction of Rate Constant for Supramolecular Systems with Multiconfigurations
JOURNAL OF PHYSICAL CHEMISTRY A, 120:981-991, FEB 2 2016
The control of supramolecular systems requires a thorough understanding of their dynamics, especially on a molecular level. It is extremely difficult to determine the thermokinetic parameters of supramolecular systems, such as drug-cyclodextrin complexes with fast association/dissociation processes by experimental techniques. In this paper, molecular modeling combined with novel mathematical relationships integrating the thermodynamic/thermokinetic parameters of a series of isomeric multiconfigurations to predict the overall parameters in a range of pH values have been employed to study supramolecular dynamics at the molecular level. A suitable form of Eyring's equation was derived and a two-stage model was introduced. The new approach enabled accurate prediction of the apparent dissociation/association (k(off)/k(on)) and unbinding/binding (k(_r)/k(r)) rate constants of the ubiquitous multiconfiguration complexes of the supramolecular system. The pyronine Y x 1 (PY) was used as a model system for the validation of the presented method. Interestingly, the predicted k(off) value ((40 +/- 1) x 10(5) s(-1), 298 K) of PY is largely in agreement with that previously determined by fluorescence correlation spectroscopy ((5 +/- 3) X 10(5) s(-1), 298 K). Moreover, the k(off)/k(on) and k(_r)/k(r) for flurbiprofen-beta-cylcodextrin and ibuprofen-beta-cyclodextrin systems were also predicted and suggested that the association processes are diffusion-controlled. The methodology is considered to be especially useful in the design and selection of excipients for a supramolecular system with preferred association and dissociation rate constants and understanding their mechanisms. It is believed that this new approach could be applicable to a wide range of ligand-receptor supramolecular systems and will surely help in understanding their complex mechanism.
