Welcome to Structure-Guided Drug Design System

What is Mol3DOpt ?



Due to the fast development of experimental techniques, solving the three dimensional structure of a protein is becoming a routine work in modern drug discovery. The knowledge of detailed protein structure information is very useful for rational drug design. An automated ligand optimization tool, making use of structure information of protein, can assist medicinal chemist for fast drug design. We herein present Mol3DOpt, a free and easy to use web server for structure-guided ligand optimization. Mol3Dopt is a powerful computational tool for rapid generation of ligand design ideas; either in scaffold hopping, bioisosteric replacing or fragment growing.


How Mol3DOpt woks ?



The user needs to provide a protein file and a ligand file, either from the RCSB PDB database or from computational methods such as molecular docking. After input, the server would generate all replaceable substructures or growing points on the input ligand. The user chooses the substructure they want to replace or the growing point they want grow and then submit. Mol3DOpt works by searching a 3D fragment database to find suitable fragments that not only meet the geometric requirements of the remaining part of the ligand, but also fit well with local protein environments. The result page of Mol3DOpt contains two main sections: Firstly, a table of all the analogues generated by fragment replacing or growing. A detailed 3D protein-ligand interaction diagram can be explored by clicking on '3DView'. Each newly designed molecule can be downloaded directly as the mol2 format. Secondly, the optimization results are provided as an xlsx file for downloading, including molecular picture and SMILES.


Ligand Design Strategy



a) Fragment Replacing by Matching Fragment Fingerprint.

This strategy works by searching the 3D fragment molecule database to find fragments with specific geometric character and atomic properties.


b) Fragment Replacing by Matching Protein environment.

This strategy works by searching the 3D protein-ligand database to find fragments bind with similar protein environment.


c) Fragment Replacing by Ring mutation.

This strategy works by replacing ring with same size, same aromaticity, but different heteroatom rings.


d) Fragment Replacing by Similarity comparison.

This strategy works by finding similar fragments through fast similarity comparison.


e) Fragment Growing by Matching Protein environment.

This strategy works by searching the 3D protein-ligand database to find fragments bind with similar protein environment.


f) Fragment Growing by Virtual Probing.

This strategy works by trying several probing groups on the growing point. Usually used for the filling of tiny pockets.

Contact

If you have any question about Mol3DOpt, please contact:

Changge Ji

Chicago.ji@gmail.com