Protein-Protein Interactions and Macromolecule Modelling Juliette - PowerPoint PPT Presentation

Protein-Protein Interactions and Macromolecule Modelling Juliette Martin Team Modelling Biological Macromolecules UMR 5086 Molecular Microbiology and Structural Biochemistry, IBCP Lyon Réunion MASIM, Paris 16 novembre 2017

Where are we ? Institut de Biologie et Chimie des Protéines Lyon UMR 5086: Molecular Microbiology and Structural Biochemistry A 10 team unit

Who are we ? Team MOBI: Modelling Biological Macromolecules Team leader Luca Monticelli Richard Lavery Guillaume Launay Juliette Martin Mélanie Garnier CR INSERM DR CNRS MdC Lyon 1 CR CNRS IE CDD

What do we do ? • Simulation of biological macromolecules : biomembranes, protein-DNA complexes, protein-protein complexes • Developments in Structural Bioinformatics : protein interface prediction, structural study of non-interacting proteins, tails in protein complexes, protein-protein docking, tools for structural bioinformatics, inference of protein-protein interaction networks

Molecular simula-ons of biomembranes Luca Monticelli MARTINI coarse-grained Biomembranes: interac=on force field development with synthe=c materials Lipid droplet biogenesis

Loic Ethève Dynamics of protein-DNA recognition Richard Lavery Juliette Martin Experimental Classical MD simulation ✓ Time-dependent recognition ✓ Essential features for stability and recognition Ethève et al NAR 2015 Ethève et al NAR 2016 Simplified rigid models Ethève et al NAR 2017

Elisa Frezza Dynamics of protein-protein complexes Juliette Martin Richard Lavery Allosteric regulation of an adenyly-cyclase by binding of regulatory G-protein mobile ATP G-protein binding Frezza et al submitted ATP locked into active conformation

Structural Bioinformatics • Protein interface prediction, • Structural study of non-interacting proteins, • Tails in protein complexes, • Protein-protein docking, • Tools for structural bioinformatics, • Inference of protein-protein interaction networks

Guillaume Launay Mélanie Garnier Protein interface prediction Juliette Martin Richard Lavery • Highly localized interac1on • Highly localized regions regions on the surface of • Enrichment in most of the proteins experimental interfaces • These regions are enriched • Computationally tractable in experimental interfaces • Original signal in • The number of probes can prediction HEX [...] 0 be reduced, without signal • Correct prediction for GPU N loss (AUC=0.64) 70% of the interfaces 25 probes Mar1n J, Lavery R: Arbitrary protein-protein docking targets biologically relevant interfaces. BMC Biophysics 2012, 5:7. Mar1n J: Benchmarking protein–protein interface predic1ons: Why you should care about protein size. Proteins 2014, 82:1444–1452.

Guillaume Launay Protein interface prediction Mélanie Garnier Juliette Martin Reille et al submitted

Guillaume Launay Non-interacting Proteins Nicoletta Ceres Juliette Martin ✓ A very common situation Interac(ng ✓ Predicted as stable by coarse- proteins grain model ✓ Major shortcuts in the native network Non-interac(ng proteins Launay, Ceres and Martin, Scientific Reports 2017

A new picture of protein-protein interactions Negative regulation 0.2% Functional interactions 9% pairs with compatible structures 99.8% Negative interactions

Tails in protein-protein complexes C elegans doi:10.1371/journal.pone.0162143.g008 ✓ Terminal residues do not ✓ Terminal residues are act as charged side chains periphery of interfaces strongly rejected at the Martin et al, PLoS ONE 2016 α Guillaume Launay Juliette Martin Olivier Martin

Guillaume Launay Protein-protein docking Mélanie Garnier Juliette Martin MEGADOCK docking engine Masahito Ohue, Tokyo Ins2tute of Technology Ongoing work….

Tools for structural bioinformatics Guillaume Launay Mélanie Garnier

Tools for structural bioinformatics

Tools for structural bioinformatics

Inference of protein-protein interactions Guillaume Launay Juliette Martin

Inference of protein-protein interactions Inference of protein-protein interactions

Inference of protein-protein interactions

Take-home message The MOBI team at IBCP is interested in: Simulation of biological ✓ Macromolecules Structural bioinformatics of ✓ Protein-Protein Interactions under various aspects

Acknowledgments MOBI team Luca Monticelli Richard Lavery Guillaume Launay Mélanie Garnier Juliette Martin juliette.martin@ibcp.fr