Package: bfee2
Binding Free Energy Estimator 2Binding free energy estimator (BFEE) is a python-based software that automates absolute binding free energy calculations through either the alchemical or geometric route by molecular dynamics simulations.Theoretical backgroundsThe degrees of freedom of the protein-ligand (or host-guest) system are described by a series of geometric variables (or collective variables), as firstly described by theKarplus group. In BFEE, a generalized, best-fit-rotation-based geometric variables are used, making it in principle available to any protein-ligand complex. Seethis paperfor introduction of these variables.In thegeometric route, the degrees of freedom is investigated one by one, through one-dimensional free-energy calculations. In BFEE,WTM-eABFis used, while other importance-sampling algorithms such asplain eABFare also acceptable.
Thealchemical routeis a variants of thedouble decoupling method (DDM). A thermodynamic cycle, in which the ligand and the geometric restraints are decoupled independently to guarantee the convergence of the simulations.这里是标准结合自由能计算方法的中文介绍.FeaturesGenerates all the input files for absolute binding free energy calculations;Perform post-treatment automatedly;Support NAMD (alchemical and geometric route) and Gromacs (geometric route) as molecular dynamics engines;Support many file formats for the input complex structure (PSF/PDB/PRM, PRM7/RST7, TOP/PDB);Support both rigid (exclude RMSD CV) and flexible (include RMSD CV) ligands and protein-protein complexes (streamlined geometrical route);...RequirementsPython 3.6+, PySide 2, numpy, scipy, matplotlib, parmed and MDAnalysis.NAMD 3.0 or later/Colvars patched Gromacs.Note: BFEE2 uses cutting-edge features of NAMD and Colvars. We highly suggest the end-user download the devel branch of NAMD fromhereand patch it withColvarsto prevent possible problems.InstallationWe suggest to install BFEE2 through conda. It will be safe if conda is install in a new environmentconda create --name bfee   (optional)
conda activate bfee        (optional)
conda install -c conda-forge BFEE2UsageSimply run BFEE2Gui.py in terminal or PowerShell. One may need to use the absolute path on MS Windows.A step-by-step tutorial is providedhere.A tutorial about new streamlined geometrical route is provided in the SI ofthis paper.CitationsWhen possible, please consider mentioningFu et al. Nat. Protoc. 2022, doi:10.1038/s41596-021-00676-1when BFEE2 is used in your project.Additional references:BFEE2:Fu et al. J. Chem. Inf. Model. 2021, 61, 2116–2123Alchemical and geometric routesGumbart et al. J. Chem. Theory Comput. 2013, 9, 794–802WTM-eABF:Fu et al. Acc. Chem. Res. 2019, 52, 3254–3264andFu et al. J. Phys. Chem. Lett. 2018, 9, 4738–4745Collective variables:Fu et al. J. Chem. Theory Comput. 2017, 13, 5173–5178Colvars module:Fiorin et al. Mol. Phys. 2013 111, 3345-3362"Mother" of all restraint-based binding free-energy calculations:Hermans et al. Isr. J. Chem. 1986, 27, 225–227Contact usTechnique issues: Haohao Fu (fhh2626@mail.nankai.edu.cn) and Haochuan Chen (yjcoshc@mail.nankai.edu.cn)This software is under theGPLv3license. For more information about the copyright of BFEE, contact the corresponding authors of the aforementioned papers (wscai@nankai.edu.cn,Christophe.Chipot@univ-lorraine.fr).