Mots-Clés

protein – RNA assemblies, molecular modeling, virtual screening, cryo-EM imaging, structural bioinformatics

Description

HOSTING LAB
The LORIA (CNRS – INRIA – Lorraine University) is an informatics and computer science lab in Nancy, France. The CAPSID team, led by Marie-Dominique Devignes, develops computational algorithms for the study of protein structures and their interactions, based on shared expertise in biological data mining, 3D modelling, docking and molecular dynamics simulation applied to macromolecular assemblies. Specific tools are developped and applied in close collaborations with several experimental biology/biophysics teams including IMoPA.

POSITION
A 12-month postdoctoral position in chemo/bio-informatics / molecular modeling is open from 01/01/2023 to 31/12/2023, renewable for (at least) 12 months thereafter. The research position is funded by the European Regional Development Fund (FEDER). The aim is the development and/or application of innovative computational tools for modeling and targeting protein – RNA assemblies, in particular with the help of cryo-EM imaging. These tools will be applied to RNA-protein complexes involved in the infection by SARS-Cov-2, in the context of a collaborative project with experimental and structural biologists (IMoPA, team 1).
Within this large project, the developments and/or applications will primarily focus on virtual screening and fragment-based drug discovery (FBDD) in multiple conformations, possibly using our chemo-informatics pipelines and experimental data of virus-host cell interactions. This point will be carried out in collaboration with HARMONIC PHARMA. Depending on the candidate’s expertise, and on possible funding extensions, the candidate could test new methodological approaches such as: (i) a multi-scale representation of protein shape variability to be implemented in our fragment-based RNA docking tools*, (ii) the inclusion of cryo-EM maps as constraints in our branch-and-bound docking tool.

* https://members.loria.fr/IsaureCB/projets/orca-3d/
** https://doi.org/10.1093/bioinformatics/btz434

MISSIONS
Structure-based virtual screening on a viral protein target
    • Literature and structural database survey for available information of the target and its druggable sites
    • Lists of candidate inhibitors and flexible docking in druggable sites
    • Search for safe drug candidates by drug repositioning (with Harmonic Pharma)

Development of computational tools
    • Conception and implementation of new docking options for RNA or small ligands on protein
    • Testing of the new docking options on known benchmarks
    • Collaboration with the team engineer to make the new methods available on our software plateform

Application to biological targets
    • Collaboration with experimentalist teams to get relevant data for the modeling
    • Application of the new methods to protein – RNA /inhibitor complexes

REQUIREMENTS

Knowledges:
- Structural biochemistry
- Structural biology
- Chemoinformatics

Skills :
- Good programming/scripting skills, preferentially in python
- Chemical modeling and docking
- Molecular modeling (incl. molecular dynamics simulation)

Soft skills:
- Fluent orally in French or English (C1 level)
- Competent in written English (B2 level)