David L. Mobley

TL;DR: This work presents a tool, alchemical-setup.py, that automatically generates all the input files needed to perform relative solvation and binding free energy calculations with the MD package GROMACS, and provides a set of simulation input parameters.

TL;DR: In this article, the rotamer rearrangements between apo and holo states of a protein are identified as crucial for binding and several approaches to obtain apo state ensembles for accurate absolute ΔG calculations are presented.

TL;DR: A new "separated topologies" method is described, which computes relative binding free energies using orientational restraints and which has several advantages over existing methods.

TL;DR: Results in this challenge tentatively suggest that further investigation of polarizable force fields for these challenges may be warranted, and one strategy for achieving reasonable accuracy was to make empirical corrections to binding predictions based on previous data for host categories which have been studied well before, though this can be of limited value when new systems are included.

TL;DR: This work examined the sensitivity of computed binding free energies to the ligand's electrostatic and van der Waals parameters and estimated that random, uncorrelated errors in force field nonbonded parameters must be smaller than 0.02 e per charge, 0.06 Å per radius, and 0.01 kcal/mol per well depth to obtain 68% confidence that a computed affinity for a moderately-sized lead compound will fall within 1 kcal/ mol of the true affinity.