SAMPL6 host-guest binding affinities and binding poses from spherical-coordinates-biased simulations.

ABSTRACT

Host-guest binding is a challenging problem in computer simulation. The prediction of binding affinities between hosts and guests is an important part of the statistical assessment of the modeling of proteins and ligands (SAMPL) challenges. In this work, the volume-based variant of well-tempered metadynamics is employed to calculate the binding affinities of the host-guest systems in the SAMPL6 challenge. By biasing the spherical coordinates describing the relative position of the host and the guest, the initial-configuration-induced bias vanishes and all possible binding poses are explored. The agreement between the predictions and the experimental results and the observation of new binding poses indicate that the volume-based technique serves as a nice candidate for the calculation of binding free energies and the search of the binding poses.