CReM: chemically reasonable mutations

This app generates structures based on a seed molecule using chemically reasonable replacement framework (CReM). It has two modes: scaffold decoration and analogs enumeration. We expect this app will support and enhance creativity of medicinal chemists to decide which modifications to make.

This app implements unsupervised structure generation. We also have software developed based on CReM for guided ligand- and structure-based design: hit expansion, lead optimization, de novo design using docking and pharmacophore models. If you are interested you may contact Dr. Pavel Polishchuk (pavlo.polishchuk@upol.cz)

1. If you select some atoms on a drawn structure, modifications will be applied only to them (to guide modifications to a region of interest). If not, all atoms will be attempted to modify.

Output SMILES:

Mode:

Fragment database: Databases prepared from compounds of ChEMBL22 with synthetic accessibility score below 2 or below 2.5. Additionally fragments were filtered by structural alerts.

Context radius: {{ contextRadius }} Radius of chemical context considered during replacement/attachment, greater radius results in more synthetically relevant modifications but less numerous.

Maximum number of replacement: {{ maxNumOfReplacements }} Number of randomly chosen modifications to apply. The number of actually applied modifications can be less (e.g. due to a small number of available fragments for certain contexts, etc).

Maximum fragment size: {{ maxFragmentSize }} Maximum size of an attached/replaced fragment.

This research was funded by ELIXIR CZ research infrastructure project (MEYS Grant No: LM2018131) and by INTER-EXCELLENCE LTARF18013 project.