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# PRODIGY / Binding Affinity Prediction
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---
PRODIGY is also available as a web service @ [wenmr.science.uu.nl/prodigy](https://wenmr.science.uu.nl/prodigy/)
## Installation
```text
pip install prodigy-prot
```
If you want to develop PRODIGY, check [DEVELOPMENT](DEVELOPMENT.md) for more details.
## Usage
You can run `prodigy` either on a single structure:
```bash
prodigy <structure_file>
```
Or in a directory containing multiple molecules:
```bash
prodigy <directory_with_molecules>
```
To get a list of all the possible options.
```bash
$ prodigy -h
usage: prodigy [-h] [--distance-cutoff DISTANCE_CUTOFF] [--acc-threshold ACC_THRESHOLD]
[--temperature TEMPERATURE] [--contact_list] [--pymol_selection] [-q]
[--selection A B [A,B C ...]]
input_path
Binding affinity predictor based on Intermolecular Contacts (ICs).
positional arguments:
input_path Path to either:
- Structure in PDB or mmCIF format
- Directory containing structure files
options:
-h, --help show this help message and exit
--distance-cutoff DISTANCE_CUTOFF
Distance cutoff to calculate ICs
--acc-threshold ACC_THRESHOLD
Accessibility threshold for BSA analysis
--temperature TEMPERATURE
Temperature (C) for Kd prediction
--contact_list Output a list of contacts
--pymol_selection Output a script to highlight the interface (pymol)
-q, --quiet Outputs only the predicted affinity value
Selection Options:
By default, all intermolecular contacts are taken into consideration,
a molecule being defined as an isolated group of amino acids sharing
a common chain identifier. In specific cases, for example
antibody-antigen complexes, some chains should be considered as a
single molecule.
Use the --selection option to provide collections of chains that should
be considered for the calculation. Separate by a space the chains that
are to be considered _different_ molecules. Use commas to include multiple
chains as part of a single group:
--selection A B => Contacts calculated (only) between chains A and B.
--selection A,B C => Contacts calculated (only) between chains A and C; and B and C.
--selection A B C => Contacts calculated (only) between chains A and B; B and C; and A and C.
--selection A B [A,B C ...]
```
## Example single structure
Download the PDB [3BZD](https://www.rcsb.org/structure/3bzd) and run PRODIGY on it.
```bash
$ curl -o 3bzd.pdb https://files.rcsb.org/download/3BZD.pdb
$ prodigy 3bzd.pdb
[+] Reading structure file: /Users/rvhonorato/dbg/3bzd.pdb
[+] Parsed structure file 3bzd (2 chains, 343 residues)
[+] No. of intermolecular contacts: 51
[+] No. of charged-charged contacts: 4
[+] No. of charged-polar contacts: 7
[+] No. of charged-apolar contacts: 6
[+] No. of polar-polar contacts: 7
[+] No. of apolar-polar contacts: 15
[+] No. of apolar-apolar contacts: 12
[+] Percentage of apolar NIS residues: 29.48
[+] Percentage of charged NIS residues: 29.48
[++] Predicted binding affinity (kcal.mol-1): -9.4
[++] Predicted dissociation constant (M) at 25.0˚C: 1.3e-07
```
Details of the binding affinity predictor implemented in PRODIGY can be found at [10.7554/elife.07454](https://doi.org/10.7554/elife.07454)
## Example multiple structures
Create a directory that will hold your input molecules
```bash
mkdir input
```
Download some molecules (or copy them into this directory):
```text
curl -o input/3bzd.pdb https://files.rcsb.org/download/3BZD.pdb
curl -o input/2oob.pdb https://files.rcsb.org/download/2OOB.pdb
curl -o input/1ppe.pdb https://files.rcsb.org/download/1PPE.pdb
```
Run `prodigy` with the `quiet` option, so it is easier to parse the output later:
```bash
$ prodigy -q input/
3bzd -9.373
2oob -6.230
1ppe -14.727
```
## Citing us
If our tool is useful to you, please cite PRODIGY in your publications:
- **Xue L, Rodrigues J, Kastritis P, Bonvin A.M.J.J, Vangone A.**: PRODIGY: a web server for predicting the binding affinity of protein-protein complexes. _Bioinformatics_ (2016) ([10.1093/bioinformatics/btw514](https://doi.org/10.1093/bioinformatics/btw514))
- **Anna Vangone and Alexandre M.J.J. Bonvin**: Contacts-based prediction of binding affinity in protein-protein complexes. _eLife_, e07454 (2015) ([10.7554/eLife.07454](https://doi.org/10.7554/elife.07454))
- **Panagiotis L. Kastritis , João P.G.L.M. Rodrigues, Gert E. Folkers, Rolf Boelens, Alexandre M.J.J. Bonvin**: Proteins Feel More Than They See: Fine-Tuning of Binding Affinity by Properties of the Non-Interacting Surface. _Journal of Molecular Biology_, 14, 2632–2652 (2014). ([10.1016/j.jmb.2014.04.017](https://doi.org/10.1016/j.jmb.2014.04.017))
## Contact
For questions about PRODIGY usage, please reach out the team at [ask.bioexcel.eu](https://ask.bioexcel.eu/)
## Information about dependencies
The scripts rely on [Biopython](www.biopython.org) to validate the PDB structures and calculate
interatomic distances. [freesasa](https://github.com/mittinatten/freesasa), with the parameter
set used in NACCESS ([Chothia, 1976](http://www.ncbi.nlm.nih.gov/pubmed/994183)), is also
required for calculating the buried surface area.
**DISCLAIMER**: given the different software to calculate solvent accessiblity, predicted
values might differ (very slightly) from those published in the reference implementations.
The correlation of the actual atomic accessibilities is over 0.99, so we expect these
differences to be very minor.
---
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