1- Scientific context and project objectives

Within the Cancéropôle, the SEESIB laboratory looks for new anti-tumour molecules, the biological targets of which may or may not be known.
Our laboratory has a significant number of chemicals and reactive intermediates whose full potential has not yet been made use of: as anti-cancer molecules.
To enhance the laboratory’s chemical library, it is possible to carry out virtual screening on the chemical compounds it contains, so as to identify those which could act on the biological targets studied at the Canceropôle.
Virtual screening involves docking studies of all the molecules in our chemical library on anti-cancer cells or targets that are of potential interest. This therefore requires a large amount of computing.
The primary aim of this project is to automate the whole docking study procedure, namely the preparation of data, storage, the docking computation and results analysis.
The project’s second aim is to construct the SEESIB Laboratory’s chemical library. The large number of molecules at the Laboratory represents many, many hours in terms of information to be entered manually.

2- Project description

Docking studies require three-dimensional (3D) structures of the biological target and molecules to be tested. The biological target 3D structures can be retrieved in the PDB (Protein Data Bank). However, we do not have any 3D structures of the compounds in the chemical library. The only information available is the structural formula*..
Part of the laboratory’s expertise involves translating this information into a 3D structure and searching for the different stable conformations* of these molecules by conformational analysis*. After obtaining the 3D structures of both systems, the actual docking can then be carried out.
At present, the longest process is generating the 3D structures of molecules by conformational analysis, as this is done “manually”.
Our project aims to automate the entire 3D structure development chain of chemical compounds:

• Retrieve information from the 2D structure contained in the chemical library,
• Carry out a conformational analysis,
• Identify the most stable conformations,
• Carry out docking computation between each of these conformations and the biological target,
• Analyse the docking scores to allow the information to be pre-processed.

Storage space for all the conformational analyses carried out must be provided to be able to reuse them on new biological targets.
The computations and storage will be carried out using the means at Auvergrid’s and the SEESIB laboratory’s disposal.
Regarding the chemical library, the base structure exists, but the data has not been entered. Since there are so many chemicals stored in it, it will take a long time to enter these compounds into the database.

3- Public or controlled use

Using virtual screening to search for new molecules that target tumours in the SEESIB Laboratory’s chemical library is the project’s aim. As a result, it will initially be necessary to control use of the tool developed in this project. But it may subsequently become available for public use.

4- Expected results

Through this project, we expect to:

• a) promote the laboratory’s chemical heritage,
• b) acquire new leads for developing molecules that target tumours,
• c) perhaps identify new biological targets through pharmacophores.
• d) set up the laboratory’s chemical library.

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