Mots-Clés

RNA GNN MD simulations, QM/MM calculations molecular modelling

Description

Context

The research activities will be conducted in the MMVRT (Molecular Mechanism of viral RNA translation) team of CiTCoM (UMR CNRS 8038, Université Paris Cité), a multidisciplinary unit with expertise in molecular modelling, biochemistry, organic chemistry, structural biology, and microbiology. The position is part of the four-year project MAGENTA (Modelling RNA structures usinG chEmical probiNg daTA) funded by ANR (Agence National de la Recherche) in the JCJC scheme started in 2023. The objective of MAGENTA is twofold: first, to understand the chemical origin of biochemical reactivity (like SHAPE that stands for Selective 2’-Hydroxyl Acylation analyzed by Primer Extension) that provides essential information at the nucleotide level, and to unveil the complex relationship between measured reactivities, local geometry of RNA, and its environment for free RNA molecules; second, to integrate this information into a newly developed theoretical and computational framework, to bias and predict RNA structures. The project is conducted in close collaboration with the experimental colleagues in the team who are experts in biochemical probing.

Position

The postdoctoral researcher will be involved in the development of a new theoretical framework to determine 3D RNA structures. To do so, he/she will study the reactivity of several chemical probes with specific RNA molecules with the aim to understand the relationship between the structure, flexibility, local geometry of RNA and the biochemical reactivity of nucleotides. To do so, QM/MM calculations and alchemical free energy calculations will be performed in combination with more standard approaches. He/she will also be involved in the definition of a graph neural network to predict the reactivity.

Requirements

Applicants must have a PhD (or are expected to defend their thesis in the next months) in Physics, Chemistry, Material Science, Computational Biology or related fields. Ideal candidates have experience in the molecular modelling of biomolecules. Experience in one or more of the following fields will be taken into account:

• Molecular dynamics simulations of nucleic acids (in particular RNA)
• QM/MM calculations to study reactivity
• Development and/or application of enhanced sampling methods
• Development and/or application of methods to combine experimental data with molecular simulations
• Alchemical free energy methods
• Machine learning methods

Starting date: Ideally the position will start in January/February 2025