These are preliminary reports that have not been peer-reviewed. They should not be regarded as conclusive, guide clinical practice/health-related behavior, or be reported in news media as established information. For more information, please see our FAQs.
SAMPL7.pdf (1.47 MB)
SAMPL7 TrimerTrip Host-Guest Binding Poses and Binding Affinities from Spherical-Coordinates-Biased Simulations
Preprints are manuscripts made publicly available before they have been submitted for formal peer review and publication. They might contain new research findings or data. Preprints can be a draft or final version of an author's research but must not have been accepted for publication at the time of submission.
revised on 25.07.2020 and posted on 27.07.2020by Zhaoxi Sun
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.