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manuscript.He.7.23.2019.chemxriv.pdf (879.85 kB)

The Role of Displacing Confined Solvent in the Conformational Equilibrium of β-Cyclodextrin

submitted on 23.07.2019, 14:22 and posted on 24.07.2019, 12:38 by Peng He, Sheila Sarkar, Emilio Gallicchio, Tom Kurtzman, Lauren Wickstrom

This study investigates the role of hydration and its relationship to the conformational equilibrium of the host molecule β-cyclodextrin. Molecular dynamics simulations indicate that the unbound β-cyclodextrin exhibits two state behavior in explicit solvent due to the opening and closing of its cavity. In implicit solvent, these transitions are not observed and there is one dominant conformation of β-cyclodextrin with an open cavity. Based on these observations, we investigate the hypothesis that the expulsion of thermodynamically unfavorable water molecules into the bulk plays an important role in controlling the accessibility of the closed macrostate at room temperature. We compare the results of the molecular mechanics analytical generalized Born plus non-polar solvation approach to those obtained through Grid Inhomogeneous Solvation Theory analysis with explicit solvation to elucidate the thermodynamic forces at play. The calculations help to illustrate the deficiencies of continuum solvent models and demonstrate the key role of the thermodynamics of enclosed hydration in driving the conformational equilibrium of molecules in solution.


NIH R01-GM100946


Email Address of Submitting Author


CUNY Borough of Manhattan Community College


United States of America

ORCID For Submitting Author


Declaration of Conflict of Interest

No conflict of interest