Modeling the Mechanism of Action of DNA Intercalators for Cancer Therapy Applications (M/F)

Job Description

Missions

Traditional anticancer chemotherapy often lacks spatial and temporal precision, leading to unintended damage to healthy tissues. An innovative alternative involves developing light-activated molecules whose cytotoxicity is triggered only upon exposure to visible or infrared light, enabling targeted, controlled therapy. This approach enhances efficacy while minimizing off-target effects.
Building on promising preliminary results (including a patent filing), we have designed novel molecules that become active upon irradiation. However, their mechanisms of activation (which depend critically on molecular substituents) remain incompletely understood. Additionally, predicting how these activated molecules interact with DNA is essential for optimizing their therapeutic potential. The person selected for this position will be responsible for improving the understanding of the mechanisms involved, using computational tools.

Activity

This postdoctoral project will address these challenges through a dual computational approach:
1/ Mechanistic Insights: Use QM/MM-MD simulations combined with free energy calculations to elucidate the activation mechanisms of these molecules.
2/ Binding Affinity Prediction: Employ MD simulations and enhanced sampling methods to predict the DNA-binding affinity of new molecules, guiding their synthesis by our collaborators.

Your Profil

Skills

PhD diploma holder, with a background in computational chemistry/biochemistry. A strong interest for QM/MM approaches and a documented experience with MD simulations applied to biological systems are required.
Good programming skills and experience with free energy calculations and enhanced sampling would be strongly appreciated.

Your Work Environment

This postdoctoral fellowship is part of the LIDICAN project, funded by INSERM, and will be carried out in collaboration with our partners, M. Boisbrun (University of Lorraine, L2CM) and M.-H. David-Cordonnier (INSERM, OncoLille), who will conduct the organic synthesis and assess the biological activity of the compounds in cell lines and animal models.
The candidate will work at the Laboratoire de Physique et Chimie Théoriques in Nancy, France, in close collaboration with a PhD student and several early-career researchers from the partner teams.

LPCT is committed to fostering a supportive and inclusive research environment. We strongly encourage applications from individuals belonging to groups traditionally underrepresented in computational and physical sciences, including women, racialized and ethnic minorities, LGBTQIA+ individuals, and persons with disabilities. Non-linear career paths will be considered positively, and reasonable accommodations can be provided throughout the recruitment process and during the contract.

Compensation and benefits

Compensation

Minimum gross salary 3,000 euros

Annual leave and RTT

44 jours

Remote Working practice and compensation

Pratique et indemnisation du TT

Transport

Prise en charge à 75% du coût et forfait mobilité durable jusqu’à 300€

About the offer

About the CNRS

The CNRS is a major player in fundamental research on a global scale. The CNRS is the only French organization active in all scientific fields. Its unique position as a multi-specialist allows it to bring together different disciplines to address the most important challenges of the contemporary world, in connection with the actors of change.

CNRS

The research professions