Stage M2S3 (2018-2019)

G-protein coupled receptors (GPCR) constitute the largest family of proteins involved in signal transduction across membranes. They also represent a major pharmaceutical class of drug targets. In the past ten years, an unprecedented number of x-ray structures of GPCR has been solved, providing structural insights on 55 orthologs. [1]
Recently, several european research groups have worked on the simulation of GPCR by molecular dynamics to investigate the relationship between structure and function and to determine which features are common to GPCR or specific of a receptor or a receptor class. [2] A total of three trajectories of 500 ns have been generated for 188 molecular systems using the same experimental conditions, in particular the composition of the lipid bilayer embedding the receptor. Data analysis has involved several laboratory. The Chemogenomics and medicinal Chemistry has focused on the recognition of drug-like ligands by the transmembrane domain.
The project consists in the determination and the analysis of ligand-receptor interactions (direct and water-mediated hydrogen bonds, ionic and aromatic interactions and hydrophobic contacts). For each the 84 studied complexes will be evaluated the frequency of all the observed interactions detected using the program IChem. [3] The all-against-all comparison of binding modes will reveal stable interaction patterns.
The candidate must show a strong interest in protein structure analysis. A well-structured and well-organised way of working is required to conduct the project. Basic programming skills in Linux environment are desirable.

[1] Structure and dynamics of GPCR signaling complexes (2018) Hilger D, Masureel M, Kobilka BK. Nat Struct Mol Biol. 25:4-12.
[2] http://open.gpcr-modsim.org/, http://www.glisten-gpcr.eu/
[3] IChem: A Versatile Toolkit for Detecting, Comparing, and Predicting Protein-Ligand Interactions (2018) Da Silva F, Desaphy J, Rognan D. ChemMedChem. 13:507-510