SENSAAS-Bioisostere

Tutorial 2: Scaffold-hopping of type 4 to optimize a macrocyclic natural product

Download the molecule molecule10.sdf
Download the bioisostere molecule14.sdf

Link to the original publication

Inputs:
Reference molecule10.sdf
Fragment to replace is number 1 in make_fgts_aggreg.sdf
Database pdb

Results
In this tutorial, results show that the molecule number 173 in ordered-bioisosteres-pdb.sdf corresponds to the bioisostere Molecule 14 in the publication but with the 3 substituents of Molecule 10

Download best aligned bioisosteres ordered-bioisosteres-pdb.sdf (229) and scores ordered-bioisosteres-pdb-score.txt (more information on scores).
To visualize superimposition results: 3Dviewer

You can install and use DataWarrior (free software) to read the SDF file content as a table (available for Windows/Linux/MacOS-X)
Note: it has been observed that the minimization of some molecular structures is not sufficient with the standard process (RDKit, MMFF94 force field, 2000 Minimization cycles). This can sometimes cause some structure distortion).

Run completed

To visualize results, you can use this webtool 3Dviewer and click to display superimposed bioisosteres