FC-Bioisostere

3D/2D Mining the PDB is worth
(100,000 3D experimental macromolecular structures)
FC-Bioisostere/MED-SuMo are a unique software package to convert observed 3D binding-pocket similarities in bioisostere replacement rules

FC-Bioisostere GUI


Replace substructures in your molecule of interest by equivalent chemical moieties in few clicks to optimize the pharmacokinetic profile:

FC-Bioisostere opens access to 3D bioisosteric replacement onto your molecule of interest to find chemical groups having similar 3D biological interactions. While maintaining target potencies, it helps Chemists to optimize additional properties in pharmacokinetics and metabolic response, and/or to escape from existing patents by selecting alternative equivalent chemical groups.

 

FC-Bioisostere, a 2 step software application:

First, users can automatically build a database of 3D bioisosteres :
  • from an input set of pre-aligned ligands (3D SD files) where pairs of 3D overlapping fragments are detected and stored ;
  • by driving MED-SuMo MEDIT SA software to extract from the PDB files (Protein Data Bank, ~90000 proteins) and/or your in-house biostructural data all local protein-ligand similar superpositions (defined by charges, Hbond, hydrophobic, aromatic, ... interactions);
  • or alternatively we provide pre-computed databases of bioisostere pairs built upon the whole PDB prepared by our experts.
Second, the input molecule of interest is deconvoluted and/or splitted in fragments (6 methods are available). Once fragments to be replaced are selected, all fitting replacement pairs of fragment are retrieved from the database. Different methods to merge/fuse those fragments into the input molecule are provided to generate full bioisosteres. 1D/2D/3D chemical and protein scoring filters help to sort/focus on the best bioisostere candidates.

Please look at the FC-Bioisostere workflow

 

Main features:

  • Access to experimental bioisosteric rules observed by mining similar protein-fragment interactions in biostructural data (Protein Data Bank) with MED-SuMo MEDIT’s technology
  • Drive MED-SuMo-server software over the whole PDB in few clicks (requires a separate license for MED-SuMo-server)
  • Generate various bioisostere databases to focus on best biostructural public/in-house material to get faster performance, or to orient around a specific protein or ligand family
  • Can be used in stand-alone mode on a simple MS-Windows computer by using pre-calculated bioisostere databases (resell by MEDIT SA)
  • 2D/3D chemical spreadsheet and 3Dviewer
  • Multiple fragmentation algorithms to deconvolute ligands and input molecule in fragments/substructures
  • Powerful filters to (1) manage in 1D/2D/3D duplicates, (2) control the chemical diversity, (3) orient the process in direction to chemical supplier library
  • Review pairs of bioisosteric fragment on your input molecule
  • Protein binding score to sort bioisosteric candidates (in case you have a protein target structure)
  • Export possible replacements and bioisosteres in SD files format
  • MS-Windows based intuitive graphical interface

A C2P component:

FC-Bioisostere software has been developed by Felix Concordia SARL through a collaboration with MEDIT SA. It's a new deliverable of the C2P consortium (Chemo-Proteomic Platform) to cross-mine altogether biostructural, structure-activities and chemical libraries data.

C2P
already includes : (a) MED-SuMo to detect/superpose 3D protein surface interactions, (b) MEDP-Fragmentor to deconvolute protein-ligand structure in pocket-fragment interactions, (c) MEDP-SiteClassifier to navigate in all intra-familly/inter-family binding site similarities across the whole PDB, (d) MED-Ligand to explore 1D/2D/3D ligand/fragment similarities, (e) MEDL-Hybridise to combine in 3D fragments, (f) MEDL-Filter to filter/score according to 1D/2D/3D (protein)-ligand propertie

 

See more in:

FC-Bioisostere case study
FC-Bioisostere workflow
FC-Bioisostere brochure

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