Chemoinformatics tools
Institute of Molecular and Translational Medicine, Palacky University
CReM-dock: generation of chemically reasonable molecules guided by molecular docking
The open-source software based on CReM and EasyDock to generate chemically reasonable molecules.
Features:
- fully automated workflow
- different selection strategies (greedy, Pareto, k-means clustering)
- different objective functions (docking score, docking score augmented with QED or the fraction of sp3-carbon atoms, docking score divided on the number of heavy atoms, etc)
- user-defined thresholds for maximum allowed physicochemical parameters (MW, logP, RTB, TPSA)
- using protein-ligand interaction fingerprints (ProLIF) and/or RMSD to a parent molecule to control the pose of a constructed ligand
- indirect control over synthetic feasibility of generated structures (based on CReM parameters)
- support docking programs integrated in EasyDock, including ligand preparation steps and distributed calculations
- output is SQLite database from which a user can retrieve all necessary information
- continue interrupted/unfinished generation by rerun of the same command
Modes:
- Hit generation Generation of molecules which starts from a set of fragment supplied as SMILES or 2D SDF. In these case the supplied fragments are docked, pass PLIF/RMSD check (optional) and best candidates are used for growing on the next iteration.
- Hit expansion Expansion of a co-crystallized ligand by supplying 3D ligand structure (SDF). In this case an input molecule is directly going to the growing stage.
Repository:
https://github.com/DrrDom/crem-dockLinks to CReM fragment databases are here
General workflow
Citation:
Minibaeva, G.; Polishchuk, P. CReM-dock: de novo design of synthetically feasible compounds guided by molecular docking. ChemRxiv 2024. - https://doi.org/10.26434/chemrxiv-2024-fpzqb-v2