https://github.com/ale94mleon/bfee2

binding free energy estimator 2

https://github.com/ale94mleon/bfee2

Repository

binding free energy estimator 2

https://github.com/ale94mleon/BFEE2/blob/main/

# Binding Free Energy Estimator 2
[![DOI](https://zenodo.org/badge/322234705.svg)](https://zenodo.org/badge/latestdoi/322234705)

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](https://pubs.acs.org/doi/abs/10.1021/jp0217839). 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](https://pubs.acs.org/doi/abs/10.1021/acs.jctc.7b00791) for introduction of these variables.


In the [geometric route](https://pubs.acs.org/doi/10.1021/ct3008099), the degrees of freedom is investigated one by one, through one-dimensional free-energy calculations. In BFEE, [WTM-eABF](https://pubs.acs.org/doi/abs/10.1021/acs.accounts.9b00473) is used, while other importance-sampling algorithms such as [plain eABF](https://pubs.acs.org/doi/abs/10.1021/acs.jctc.6b00447) are also acceptable.
The [alchemical route](https://pubs.acs.org/doi/10.1021/ct3008099) is a variants of the [double decoupling method (DDM)](https://www.sciencedirect.com/science/article/pii/S0006349597787563). A thermodynamic cycle, in which the ligand and the geometric restraints are decoupled independently to guarantee the convergence of the simulations.

[](http://sioc-journal.cn/Jwk_hxxb/CN/10.6023/A20100489).


## 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, scipy, matplotlib, parmed and MDAnalysis.

[NAMD 3.0 or later](https://www.ks.uiuc.edu/Development/Download/download.cgi?PackageName=NAMD) / [Colvars patched Gromacs](https://github.com/Colvars/colvars).

**Note: BFEE2 uses cutting-edge features of NAMD and Colvars. We highly suggest the end-user download the devel branch of NAMD from [here](https://gitlab.com/tcbgUIUC/namd/-/tree/devel) and patch it with [Colvars](https://github.com/Colvars/colvars) to prevent possible problems.**

## 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](https://www.nature.com/articles/s41596-021-00676-1).


## Citations
When possible, please consider mentioning [Fu et al. Nat. Protoc. 2022, doi:10.1038/s41596-021-00676-1](https://www.nature.com/articles/s41596-021-00676-1#citeas) when BFEE2 is used in your project.


Additional references:

BFEE2: [Fu et al. J. Chem. Inf. Model. 2021, 61, 21162123](https://pubs.acs.org/doi/abs/10.1021/acs.jcim.1c00269)

Alchemical and geometric routes [Gumbart et al. J. Chem. Theory Comput. 2013, 9, 794802](https://pubs.acs.org/doi/abs/10.1021/ct3008099)

WTM-eABF: [Fu et al. Acc. Chem. Res. 2019, 52, 32543264](https://pubs.acs.org/doi/abs/10.1021/acs.accounts.9b00473) and [Fu et al. J. Phys. Chem. Lett. 2018, 9, 47384745](https://pubs.acs.org/doi/abs/10.1021/acs.jpclett.8b01994)

Collective variables: [Fu et al. J. Chem. Theory Comput. 2017, 13, 51735178](https://pubs.acs.org/doi/abs/10.1021/acs.jctc.7b00791)

Colvars module: [Fiorin et al. Mol. Phys. 2013 111, 3345-3362](https://www.tandfonline.com/doi/full/10.1080/00268976.2013.813594)

"Mother" of all restraint-based binding free-energy calculations: [Hermans et al. Isr. J. Chem. 1986, 27, 225227](https://onlinelibrary.wiley.com/doi/abs/10.1002/ijch.198600032)


## Contact us
Technique issues: Haohao Fu (fhh2626@mail.nankai.edu.cn) and Haochuan Chen (yjcoshc@mail.nankai.edu.cn)


This software is under the [GPLv3](https://www.gnu.org/licenses/gpl-3.0.en.html) license. 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).

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