BFEE2: Automated, Streamlined, and Accurate Absolute Binding Free-Energy Calculations

Accurate absolute binding free-energy
estimation in silico, following either an alchemical
or a geometrical route, involves
several subprocesses and requires the introduction of geometric restraints.
Human intervention, for instance, to define the necessary collective
variables, prepare the input files, monitor the simulation, and perform
post-treatments is, however, tedious, cumbersome, and prone to errors.
With the aim of automating and streamlining free-energy calculations,
especially for nonexperts, version 2.0 of the binding free energy
estimator (BFEE2) provides both standardized alchemical and geometrical
workflows and obviates the need for extensive human intervention to
guarantee complete reproducibility of the results. To achieve the
largest gamut of protein–ligand and, more generally, of host–guest
complexes, BFEE2 supports most academic force fields, such as CHARMM,
Amber, OPLS, and GROMOS. Configurational files are generated in the
NAMD and Gromacs formats, and all the post-treatments are performed
in an automated fashion. Moreover, convergence of the free-energy
calculation can be monitored from the intermediate files generated
during the simulation. All in all, BFEE2 is a foolproof, versatile
tool for accurate absolute binding free-energy calculations, assisting
the end-user over a broad range of applications.