Masatake Sugita
Ritsumeikan University, Japan
Title: Predicting the binding free energy of the inclusion process of Cyclodextrin deriveatives and small molecules by means of MM/3D-RISM method
Biography
Biography: Masatake Sugita
Abstract
Cyclodextrin is a cyclic molecule formed by six to eight glucopyranose units and include a small hydrophobic molecule into a cavity. Cyclodextrins are widely used as a additive of foods and drugs, because cyclodextrins have low toxicity and its physicochemical characteristics can be varied by the substitution of hydroxyl group. Although rational design of cyclodextrin derivatives are desired to develop a new pharmaceutical products based on inclusion ability of the cycrodextrins, designing of a functional Cyclodextrin derivative have been practiced in an empirical way so far. In this study, we tried to develop a procedure based on MM/3D-RISM method to screen drug candidate cyclodextrin derivative and assessed the capability of our procedure on the test system, for instance, 2-Hydroxypropyl-β-Cyclodextrin and small molecules. To accomplish this objective, we tried to get appropriate ensemble of the complex state and isolated state, and, after that, predict the binding free energy. Our procedure reproduce reasonable correlation between the experimental and calculated binding free energy and we conclude MM/3D-RISM method have an ability to distinguish the tightly bind compounds from the candidate molecules if we get an appropriate ensemble. Now we are applying this procedure to screen a functional cyclodextrin derivative. We are also trying to improve our procedure.
