Mots-Clés

bioinformatique structurale, coévolution, AlphaFold2, pipeline computationnel, développement de logiciels

Description

M2 Project: Predicting Alternative Protein Conformations Using AlphaFold 2

Supervisor:
Diego Javier ZEA, Molecular Assemblies and Genome Integrity, I2BC, diego.zea@i2bc.paris-saclay.fr

Summary:
Proteins are dynamic molecules that adopt multiple conformations to perform their biological functions. Predicting these alternative structures represents a significant challenge in computational biology, particularly for flexible and multidomain proteins. This M2 stage project is part of the ANR-funded SPPICES (Scoring and Predicting Protein Interactions and Conformations based on Evolutionary Signals) project, which aims to predict protein conformations and protein-protein interactions by leveraging state-of-the-art modeling tools like AlphaFold 2 (AF2) and evolutionary signals on multiple sequence alignments (MSAs).

The specific goal of this M2 project is to develop an automated pipeline that can predict alternative conformations of proteins using structural templates and to assess the role of evolutionary signals in guiding AF2 predictions. This involves developing methods to extend the conformational space explored by AF2 and optimizing MSAs to improve model outcomes. 

During this internship, the student will optimize the pipeline for automated selection of structural templates and efficient MSA generation, focusing on increasing the diversity of predicted protein conformations. The outcome will be a comprehensive tool for predicting protein conformations, which will interest the broader scientific community.

Expected Skills:
The candidate should have a background in bioinformatics or a related field and strong programming skills. The pipeline is being developed using the Julia programming language, so programming in Julia is a plus. Familiarity with the Linux terminal and Git is desirable. Problem-solving skills and the ability to work independently are also desirable.

Possibility of Funding:
The student will receive a monthly stipend for up to six months. There is a possibility to continue with a funded PhD thesis, depending on the project's progress and the intern's interest.

Applications:
Please send an email containing your CV and a cover letter to Diego ZEA (diego.zea@i2bc.paris-saclay.fr), indicating in the subject "Candidate for SPPICES M2 Project"