SAMPL7 TrimerTrip host-guest binding poses and binding affinities from spherical-coordinates-biased simulations

Area of Science:

• Computational chemistry
• Molecular modeling
• Supramolecular chemistry

Background:

• Host-guest binding is a significant challenge in computational modeling.
• The SAMPL7 challenge introduced new host-guest systems, including the TrimerTrip host with 16 diverse guests.

Purpose of the Study:

• To retrospectively evaluate a computational protocol for analyzing the TrimerTrip host-guest systems from the SAMPL7 challenge.
• To investigate the binding poses and affinities of various guests to the TrimerTrip host.

Main Methods:

• Utilized spherical coordinates as collective variables coupled with metadynamics for enhanced sampling.
• Initiated simulations from random configurations to identify binding poses and estimate free energies.
• Employed a retrospective analysis of the SAMPL7 host-guest systems.

Main Results:

• Calculated binding affinities showed good agreement with experimental data.
• Successfully identified plausible binding poses for the TrimerTrip host-guest systems.
• The protocol yielded converged free energy estimates.

Conclusions:

• The employed computational protocol is effective for studying host-guest binding, including pose searching and affinity calculation.
• The identified binding poses provide a valuable starting point for further advanced free energy calculations.
• This retrospective study validates the robustness of the metadynamics approach in host-guest systems.