Société Française de Bioinformatique

Mots-Clés

RNA, binding pockets

Description

RNA is an emerging target for drug discovery and the study of RNA macro molecules has been brought under the spotlight by the recent SARS-CoV-2 pandemic.
A focus of our research group is to develop an approach for the exploration of RNA molecules to guide drug design and select potential candidates for the formation of a stable complex with a drug. This goal requires on the one hand to characterize the ensemble of structures adopted by a given RNA sequence, and, on the other, characterization of RNA-ligand interactions by defining profiles of RNA binding sites and of corresponding ligands using the increasing experimental RNA structural information available.
The aim of this project is to develop a structure-based binding site predictor using our recently introduced Statistical Molecular Interaction Fields to identify druggable RNA binding sites in and to investigate the formation of RNA/ligand complexes in the context of the molecule’s energy landscape. In particular we will focus on the simulations of aptamers for which our experimental collaborators will provide binding data from chemical probing experiments.
To this end, the postdoc will setup and analyze simulations of RNA molecules both in the absence and in the presence of a small ligand using both atomistic and coarse-grained simulations, using a variety of enhanced sampling techniques (replica exchange, discrete path sampling, ratchet simulations), and continue the development of our binding site predictor to be applied to ensembles of structures detected in simulations.
The work is part of a large project on the characterization of RNA polymorphism in relation to drug design and will be done in close collaboration with an experimental team in Paris (CiTCoM laboratory), one in King’s College London (Randal Center for Molecular Biology).
We are looking for candidates preferably at a first postdoc experience after their Ph.D. with a degree in computational biophysics, theoretical chemistry, or computational biology, with good programming skills in python and experience in running molecular simulations with common tools (gromacs, amber, namd, openmm). Previous experience in research on nucleic acids is a plus, but not strictly necessary.
The fellowship will cover 20 months of postdoc and various applications will be deposited over the next year to look for funding to extend the fellowship further. The net salary will be of about 2400 euros/month plus pension and unemployment benefits and social security (health care).
The beginning of the fellowship should be no later than October 2025.