Molecular Dynamics Study of β-Cyclodextrin-Phenylalanine (1:1) Inclusion Complex in Aqueous Medium

Atomistic molecular dynamics (MD) simulations of host guest inclusion complexes of beta-cyclodextrin (BCD) and zwitterionic phenylalanine (zPHE) following two possible orientations of zPHE in aqueous solutions have been carried out. The guest induced structural changes of BCD and the microscopic properties of surrounding water have been explored. The results obtained for the complex molecules were compared with those obtained for free BCD and free zPHE molecules. It is found that irrespective of the orientation, the complexation of BCD and zPHE (1:1) is associated with loss of configurational entropy. Besides, the net configurational entropy is found to differ depending upon its orientation inside the BCD cavity. Interestingly, within the simulation length scale it is found that the relatively hydrophobic aromatic moiety of zPHE prefers to stay within the hydrophobic cavity of BCD, irrespective of its orientation. Further, nonuniform distribution and altered tetrahedral ordering of hydration water molecules around the complex molecules as compared to that around the free forms are correlated well with their conformational flexibilities.