3dechem/kripodb repository overview

⁠Kripo DB

Library to interact with Kripo fragment, fingerprint, pharmacophore and similarity data files.

Use kripo⁠ to generate fragments, pharmacophores and fingerprints from PDB files.

KRIPO stands for Key Representation of Interaction in POckets, see reference⁠ for more information.

⁠Glossary

• Pocket, binding site of the ligand in the protein of a crystal structure
• Fragment, part of the ligand
• Subpocket, part of the protein pocket which binds with the fragment
• Fingerprint, fingerprint of structure-based pharmacophore of subpocket
• Similarity matrix, similarities between all fingerprint pairs calculated using the modified tanimoto similarity index
• Kripo fragment identifier, used as identifier for fragment, subpocket and fingerprint

⁠Install

Requirements:

• RDKit, http://www.rdkit.org/docs/Install.html⁠, to read SDF files and generate smile strings from molecules
• pip, version 8.0.0 or greater, for wheel support
• git, to clone kripodb repository during installation

pip install -U setuptools
pip install numpy
pip install git+https://github.com/3D-e-Chem/kripodb.git

⁠Usage

To see available commands

kripodb --help

⁠Create all

Commands to create all data files see update documentation⁠.

⁠Search for most similar fragments

Command to find fragments most similar to 3kxm_K74_frag1 fragment.

kripodb similar sim_all.h5 3kxm_K74_frag1 --cutoff 0.45

⁠Create similarity matrix from text files

Commands to create similarity matrix see update documentation⁠.

⁠Data sets

⁠Example

An example data set included in the data/⁠ directory of this repo. See data/README.md⁠ for more information.

⁠GPCR

All fragments based on GPCR proteins compared with all proteins in PDB.

• kripo.gpcrandhits.sqlite - Fragments sqlite database
• kripo.gpcr.h5 - HDF5 file with similarity matrix

The data set has been published at

⁠Protein Data Bank

All fragments form all proteins-ligand complexes in PDB compared with all.

• Fragments sqlite database - Download from http://3d-e-chem.vu-compmedchem.nl/kripodb/fragments.sqlite⁠
• Pharmacophores database - Download from http://3d-e-chem.vu-compmedchem.nl/kripodb/pharmacophores.h5⁠
• Similarity matrix - Can be queried on webservice at http://3d-e-chem.vu-compmedchem.nl/kripodb⁠. For build instructions see http://kripodb.readthedocs.io/en/latest/data-update.html⁠
• Fragment fingerprints - See http://kripodb.readthedocs.io/en/latest/data-update.html⁠ for instructions how to convert to a similarity matrix

Date at which the data of the 3d-e-chem.vu-compmedchem.nl webservice was last updated can found at http://3d-e-chem.vu-compmedchem.nl/kripodb/version.txt⁠

A data set with PDB entries till 23 December 2015 has been published at

⁠KNIME

The Knime-KripoDB-example.zip⁠ file is an example workflow showing how to use KripoDB python package inside KNIME (http://www.knime.org⁠). It can be run by importing it into KNIME. Make sure the Python used by KNIME is the same as the Python with kripodb package installed.

The https://github.com/3D-e-Chem/knime-kripodb⁠ repo adds KripoDB code templates to KNIME.

⁠Development of KripoDB

Install the development deps with:

pip install -r requirements.txt

⁠Docker

⁠Create image

docker build -t 3dechem/kripodb .

⁠Run container

Show the kripodb help with

docker run --rm 3dechem/kripodb kripodb --help

To calculate the mean bit density of the fingerprints in the fingerprints.sqlite file in the current working directory use following command.

docker run --rm -u $UID -v $PWD:/data 3dechem/kripodb kripodb meanbitdensity /data/fingerprints.sqlite

⁠Web service

The Kripo data files can be queried using a web service.

Start webservice with:

kripodb serve data/similarities.h5 data/fragments.sqlite data/pharmacophores.h5

It will print the urls for the swagger spec and UI.

Note! The webservice returns a limited amount of results. To get all results use local files.

On http://3d-e-chem.vu-compmedchem.nl/kripodb/ui/⁠ there is a KripoDB webservice with the full PDB fragment all vs all matrix. The date of the latest PDB record included in the webservice can be found in http://3d-e-chem.vu-compmedchem.nl/kripodb/version.txt⁠

⁠Documentation

API and data update pipeline documentation can be found at http://kripodb.readthedocs.io/en/latest/⁠.

⁠Reference

KRIPO – a structure-based pharmacophores approach explains polypharmacological effects; Tina Ritschel, Tom JJ Schirris, and Frans GM Russel; J Cheminform. 2014; 6(Suppl 1): O26; Published online 2014 Mar 11; http://dx.doi.org/10.1186/1758-2946-6-S1-O26⁠