(508e) Validation of Biomolecular Force Fields Regarding Structural and Thermodynamic Properties of Cyclodextrins and Their Complexes

Cyclodextrins, CyDs, are macrocyclic oligosugars most commonly composed of 6, 7, or 8 glucosidic units bearing the names α-, β-, and γ-CyD. Other, usually smaller, molecules (called guests) can enter their cavity forming inclusion complexes with these hosts. As a result of this complexation CyDs are widely used in many industrial products, technologies and analytical methods. [1]

CyDs have also been extensively studied by means of molecular dynamics simulations, concentrating on structural properties and / or free energies of complex formation. In the present work CyDs as well as their complexes with small organic molecules, i.e. alcohols and ketones, are studied with different biomolecular force fields in aqueous solution [2]. The evaluation is based on structural properties from crystallographic X-ray and solution NMR data as well as on experimental binding constants. Two approaches were employed to compute standard binding free enthalpies, the alchemical double decoupling method and the potential of mean force method, respectively [3]. Based on this analysis recommendations for biomolecular force fields and simulation protocols are provided that allow for a robust and efficient calculation of binding affinities.

[1] H. Dodziuk, Rigidity versus flexibility. A review of experimental and theoretical studies pertaining to the cyclodextrin nonrigidity, J. Mol. Struct., 614 (2002), pp 33-45.

[2] J. Gebhardt, N. Hansen, Calculation of binding affinities for linear alcohols to α-cyclodextrin by twin-system enveloping distribution sampling simulations, Fluid Phase Equilib., 422 (2016), pp 1-17.

[3] Y. Deng, B. Roux, Computations of standard binding free energies with molecular dynamics simulations, J. Phys. Chem. B 113 (2009) 2234-2246.