Host-guest inclusion complexes are useful models for understanding the structural and energetic aspects of molecular recognition. Due their small size relative to much more complex protein-ligand systems, converged results can be obtained rapidly for these systems thus offering the opportunity to reliably study fundamental aspects of the thermodynamics of binding. We have performed an extensive binding affinity survey of �-cyclodextrin (CD) host guest systems using the binding energy distribution analysis method (BEDAM) with implicit solvation (OPLS-AA/AGBNP2). Interestingly, we find that binding free energies are superior ranking predictors for a subset of flexible guests, whose affinities are characterized by a subtle balance between intermolecular interactions and desolvation, and energetic strain and entropic driving forces. In addition, we compare the continuum modeling of structural waters to the results obtained using Inhomogeneous fluid Solvation Theory in order to assess and improve the accuracy of our solvation model during binding.

Large scale binding affinity calculations of cyclodextrin host-guest complexes: Understanding the role of reorganization and solvation in the molecular recognition process

245th National Meeting (2013)

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