SAMPL7 TrimerTrip Host-Guest Binding Poses and Binding Affinities from Spherical-Coordinates-Biased Simulations

06 April 2020, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


Host-guest binding remains a major challenge in modern computational modelling. The newest 7th statistical assessment of the modeling of proteins and ligands (SAMPL) challenge contains a new series of host-guest systems. The TrimerTrip host binds to 16 structurally diverse guests. Previously, we have successfully employed the spherical coordinates as the collective variables coupled with the enhanced sampling technique metadynamics to enhance the sampling of the binding/unbinding event, search for possible binding poses and predict the binding affinities in all three host-guest binding cases of the 6th SAMPL challenge. In this work, we employed the same protocol to investigate the TrimerTrip host in the SAMPL7 challenge. As no binding pose is provided by the SAMPL7 host, our simulations initiate from randomly selected configurations and are proceeded long enough to obtain converged free energy estimates and search for possible binding poses. The predicted binding affinities are in good agreement with the experimental reference, and the obtained binding poses serve as a nice starting point for end-point or alchemical free energy calculations.


Free Energy Simulation
Enhanced Sampling
Binding Poses
Binding Affinities
Spherical Coordinate
Reaction Coordinate
Collective Variable
Contact Number
Free Energy Landscape
Molecular Dynamics


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