(174u) Understanding Binding Behavior in Host-Guest Systems Using Advanced Sampling Simulations

Host-guest complexes are useful for applications in biomaterials science and engineering, including drug delivery, separations, transport regulation, and novel hydrogels. Highly-specific binding interactions are a key feature of such systems, and as such knowledge of systems' binding affinity is critical. Here, we propose to use advanced sampling techniques to explore free energy landscapes of host-guest systems due to their ability to quickly sample the full phase space. We apply these methods to calculation of binding affinities between an array of small molecules and curcurbit[n]uril hosts, and compare to published results, demonstrating how unrestrained advanced sampling methods are able to determine binding affinities extremely accurately when compared to standard restraint application or thermodynamic integration methods. We also discuss how such methods might be generalized to more complex systems of interest in the biomolecular and materials simulations communities.