  Alchemical Grid Dock (AlGDock) is open-source software designed to compute
the binding potential of mean force (BPMF) - the binding free energy between a
flexible ligand and a rigid receptor - for a small organic ligand and a
biological macromolecule. Multiple BPMFs can be used to rigorously compute
binding affinities between flexible partners. AlGDock uses replica exchange
between thermodynamic states at different temperatures and receptor-ligand
interaction strengths. Receptor-ligand interaction energies are represented by
interpolating precomputed grids. Thermodynamic states are adaptively
initialized and adjusted on-the-fly to maintain replica exchange rates. In
demonstrative calculations, when the bound ligand is treated as fully solvated,
AlGDock estimates BPMFs with a precision within 4 kT in 65% and within 8 kT for
91% of systems. It correctly identifies the native binding pose in 83% of
simulations. Performance is sometimes limited by subtle differences in the
important configuration space of sampled and targeted thermodynamic states.
