Host-guest systems serve as important biological and chemical systems that have numerous applications ranging from pharmaceutical therapeutics, cosmetic formulations to chemical sensors among others. Understanding the interactions between host and guest molecules is required to facilitate the design and optimization of host-guest complexes for practical use. Computational methods can be used to predict binding affinities of guest molecules targeting a host molecule on a short time scale and low cost compared to experimental techniques. However, even the most sophisticated free energy prediction methods, such as free energy perturbation, have limited accuracy with respect to the description of simple host-guest systems such as cyclodextrin related systems. During the study of protein systems, we developed a functional group mapping approach based on explicit solvent all-atom molecular dynamics simulations (SILCS: Site Identification by Ligand Competitive Saturation) which intrinsically considers molecular flexibility and desolvation effects along with solute-host interactions. In the current study, we applied this method to study a range of cyclodextrin based host-guest systems with known experimental affinity data. SILCS is first verified to be able to map the binding patterns within and around the cyclodextrin molecule based on visual inspection of SILCS FragMaps. Docking studies of guest molecules based on the SILCS-MC protocol show a similar or better correlation between predicted and experimental affinities compared to other free energy prediction methods, but at a much lower computational cost. This result indicates that the SILCS method has the ability to qualitatively and quantitatively inform the study of host-guest systems.

Host-Guest Interactions Studied using the Site-Identification by Ligand Competitive Saturation (SILCS) Method

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.