SENSAAS-Bioisostere

Tutorial 4: Scaffold-hopping of type 4 to optimize inhibitors of KRAS

Download Molecule MRTX1133: 7t47_B_6IC.sdf extracted from the PDB complex 7T47
Download the bioisostere molecule30.sdf
Download the bioisostere molecule9.sdf

Link to the original publication

Results

Inputs:
Reference 7t47_B_6IC.sdf
Fragment to replace is number 3 in make_fgts_aggreg.sdf
Database pdb2

Results
In this tutorial, results show that the molecule number 100 in ordered-bioisosteres-pdb2.sdf corresponds to a very similar structure of the molecule 30 in the publication

Download best aligned bioisosteres ordered-bioisosteres-pdb2.sdf (399) and scores ordered-bioisosteres-pdb2-score.txt (more information on scores). Bioisosteres with a score between 0 and 1 are discarded. Some calculated properties (molecular weight, H-Acceptors, H-Donors and MolLogP) can be found in the data blocks of the SDF file.
The analysis of the frameworks and the subsequent clustering of the results can be found at clusters.html
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