Protein-Peptide Interactions
Proteins play a key role in almost all cellular functions. These macromolecules rarely act in isolation, but within complex interaction networks. Recent methods of characterizing protein-protein interactions (PPI) have made it possible to obtain high-throughput data on these interaction networks. These protein-protein interactions act usually via large interfaces (1500-3000 Å2) with no well-defined binding pocket.
The modulation of these PPIs has many therapeutic applications, but the physical characteristics of these interfaces make the rational design of inhibitors difficult. The use of peptide ligands mimicking a portion of the interaction surfaces overcomes these difficulties. These molecules are also used in a natural way, indeed peptide-protein interactions represent 15 to 40% of all cellular interactions.
These polymers have a high potential for therapeutic applications, so it is not surprising that many numerical tools have been developed to predict the structure of peptide-protein complexes.
To tackle the challenges of peptide-protein interactions we use extensive molecular dynamic (MD) simulation of multiple peptide fragments with target proteins, and thus propose a breakthrough to overcome the major limitations of current approaches.
By using high precision physics-based approach, I intend to (i) identify peptide binding sites and especially key hotspots (ii) characterize hot spots peptide sequence specificity (iii) fold a target peptide in the best ranked binding sites and ultimately (iv) optimize the peptide sequence or predict de novo optimal peptide composition.
Gromacs_py
Gromacs_py is an open source python library allowing a simplified use of the gromacs MD simulation software. Gromacs_py can build topologie based on a pdb file, create the simulation system (box, add water and ions) and run minimisation, equilibration and production. One of the main objective of the gromacs_py wrapper is to automatize routine operations for MD simulation of multiple systems.
Synthetic Channels
Collaborations:- Mihail Barboiu European Institute of Membranes, Montpellier
- Marc Baaden IBPC, Paris
- Fabio Sterpone IBPC, Paris
A collaboration with a teams of chemists, the team of Mihail Barboiu, specialized in the design of materials mimicking the membrane functions (European Institute of Membranes, Montpellier). Inspired by the aquaporin and proton channel M2 of the influenza A virus, our collaborators synthesized a molecule to allow the selective transport of water molecules through the membrane. In the long term the aim of this project is to develop synthetic molecules for the purification and desalinization of water at lower cost.
Pentameric Channels
Collaborations:- Pluton Pullumbi Air Liquide, Jouy en Josas
- Marc Baaden IBPC, Paris
Pentameric ligand-gated ion channels (pLGIC) are essential components of cell-cell communications in the nervous system; their channel opens upon the binding of a neurotransmitter (gating mechanism) and lets ions flow through the pore down the electrochemical gradient (permeation). Understanding this transition is crucial as potentiating molecules such as anesthetics and recreational drugs are believed to affect transition barriers or the relative free energy of states.
This work focuses on GLIC, a prokaryotic homologue, the structure of which has been solved in three distinct functional states. Using molecular dynamics (MD) simulations reaching an aggregated time of 100 microseconds, we aim to characterize the transition between the different states, and how it can be modulated.
