PhD position at the Enzyme and Cell Engineering Lab of the University of Picardie, Amiens, France
Because CPP/membrane recognition and translocation are slow processes, two simulation techniques will be combined to obtain accurate yet computationally cost-effective simulations: coarse-graining, which represents atom groups as pseudoparticles (limiting computational cost), and enhanced sampling, which accelerates transitions along user-defined collective coordinates related to the process under study and yields the associated free energy penalties. These collective coordinates will be carefully chosen to account both for peptide flexibility and membrane deformation, based on previous work in the lab.3 We will especially focus on two crucial phases of the global mechanism: the adsorption of the peptide on the membrane, and the first steps of its translocation through it. The studied peptides will be chosen as variations on the sequence of well-known naturally-occurring CPPs (Tat, penetratin...), as well as exemplars of the main classes of CPPs selected using the ADAPTABLE antimicrobial peptide (AMP) database hosted in the lab.4 Novel hybrid CPPs studied in the lab as part of a collaborative project with microbiologists will also be considered, providing stimulating interactions between experiments and in silico predictions. If
time allows, the simulation results will be confirmed in the lab by experimental techniques (NMR, fluorescence). Beyond the mechanisms specific to each CPP, which are valuable per se, we hope to derive guidelines facilitating the choice of CPP sequences for a given application.
Deadline for application: 1 June 2023