bfee2 3.1.1.post1

Binding Free Energy Estimator 2

Binding Free Energy Estimator 3

Binding free energy estimator 3 (BFEE3) has come! There are three major upgrades in BFEE3: (1) LDDM, a high-throughput alchemical route for absolute binding free-energy calculations; (2) streamlined geometrical route for protein-protien binding free-energy calculations and (3) quick settings for common calculations.

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 backgrounds

The 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 the Karplus group. In BFEE, a generalized, best-fit-rotation-based geometric variables are used, making it in principle available to any protein-ligand complex. See this paper for introduction of these variables.

In the geometric route, the degrees of freedom is investigated one by one, through one-dimensional free-energy calculations. In BFEE, WTM-eABF is used, while other importance-sampling algorithms such as plain eABF are also acceptable. The alchemical route is a variants of the double 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.

Features

Generates all the input files for absolute binding free energy calculations;
Support Protein-protein and protein-ligand complexes;
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);
...

Requirements

Python 3.6+, PySide 2, numpy, scipy, matplotlib, parmed and MDAnalysis.
NAMD 3.0 or later / GROMACS 2024 or later.
Note: Since both NAMD and Gromacs have incorporated Colvars in their latest binaries. Each release of BFEE3 corresponds to a version of NAMD/Gromacs. Please always use the corresponding or later versions of the MD engines for free-energy calculations!

Installation

We suggest to install BFEE through conda. It will be safe if conda is install in a new environment

conda create --name bfee   (optional)
conda activate bfee        (optional)
conda install -c conda-forge BFEE2

IMPORTANT: Please force numpy<2.3 when install BFEE because a recent update of numpy has broken parmed(https://github.com/ParmEd/ParmEd/issues/1406).

Usage

Simply run BFEE2Gui.py in terminal or PowerShell. One may need to use the absolute path on MS Windows.
A step-by-step tutorial is provided here.
A tutorial about new streamlined geometrical route is provided in the SI of this paper.

Test files

One can download the Supplement Data here for testing BFEE3.

Citations

When possible, please consider mentioning Fu et al. Nat. Protoc. 2022, doi:10.1038/s41596-021-00676-1 when BFEE is used in your project.

Additional references:
BFEE2: Fu et al. J. Chem. Inf. Model. 2021, 61, 2116–2123
BFEE2 for protein-protein binding free energy calculations Fu et al. J. Chem. Inf. Model. 2023, 63, 2512–2519
Alchemical and geometric routes Gumbart et al. J. Chem. Theory Comput. 2013, 9, 794–802
WTM-eABF: Fu et al. Acc. Chem. Res. 2019, 52, 3254–3264 and Fu et al. J. Phys. Chem. Lett. 2018, 9, 4738–4745
Collective variables: Fu et al. J. Chem. Theory Comput. 2017, 13, 5173–5178
Colvars 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, 225–227

Contact us

This software is under the GPLv3 license. For more information about BFEE, contact Haohao Fu ([e-mail]) and Haochuan Chen ([e-mail]).