kalyan-immadisetty/bfee2

binding free energy estimator 2

Binding Free Energy Estimator 2

Binding 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 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;
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);
...

Requirements

Python 3.6+, PySide 2, numpy, matplotlib and MDAnalysis.
NAMD 3.0 or later / Colvars patched Gromacs.

Installation

We suggest to install BFEE2 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

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.

Citations

When possible, please consider mentioning Fu et al. Nat. Protoc. 2022, doi:10.1038/s41596-021-00676-1 when BFEE2 is used in your project.

Additional references:
BFEE2: Fu et al. J. Chem. Inf. Model. 2021, 61, 2116–2123
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

Technique issues: Haohao Fu ([email protected]) and Haochuan Chen ([email protected])

This software is under the GPLv3 license. For more information about the copyright of BFEE, contact the corresponding authors of the aforementioned papers ([email protected], [email protected]).