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Accueil du site > Jobs - PostDoc - These > PhD opening in Paris : Advanced molecular dynamics simulations of ribosome structure and function

PhD opening in Paris : Advanced molecular dynamics simulations of ribosome structure and function

par Nord & Ile de France - 4 mars

Fully-funded PhD opening in Paris : Advanced molecular dynamics simulations of ribosome structure and function Contacts and supervisors : Jean-Philip Piquemal, Lab. de Chimie Théorique, Sorbonne Université, Paris, jean-philip.piquemal@sorbonne-universite.fr Thomas Simonson, Lab. de Biochimie, Ecole Polytechnique, Palaiseau, thomas.simonson@polytechnique.fr Accurate molecular dynamics (MD) simulations represent an important goal to understand and engineer large biomolecular complexes. An important example is the ribosome, the protein-RNA machine that carries out protein synthesis and is the target of about half of clinically-used antibiotics. A major hurdle is to accurately represent electrostatic interactions, by developing and applying energy functions that provide a sophisticated representation, such as the Amoeba polarizable force field. With such an advanced force field and large system, massively parallel software is needed, like the Tinker-HP package one of us co-develops. The thesis will focus on ribosomal structure and dynamics, including interactions with antibiotic and antimicrobial peptides. Polarizable free energy simulations will be used to understand and design the interactions and propose more effective ligands. Advanced MD methods such as Replica Exchange MD and adaptive umbrella sampling will be developed and applied, to ensure adequate sampling of conformations and converged free energies.

The position is suitable for a highly motivated student trained in physical chemistry, theoretical chemistry, biochemistry, biophysics, or a related field. It is available for 3 years, starting next fall. Applications will be accepted until the position is filled. Please send a CV and names of references to both contacts.

Selected references : Aleksandrov, Simonson (2008) JACS, 130:1114. Molecular dynamics simulations of the 30S ribosomal subunit reveal a preferred tetracycline binding site. Li, Wang, Dalby, Lagardère, Piquemal, Ponder, Ren (2017) J Comp Chem 38:2047. Tinker‐OpenMM : Absolute and relative alchemical free energies using AMOEBA on GPUs. Lipparini, Lagardère, Stamm, Cancès, Schnieders, Ren, Maday, Piquemal (2014) J Chem Theory Comp 10:1638. Scalable evaluation of polarization energy and associated forces in polarizable molecular dynamics : I. Toward massively parallel direct space computations. Lagardère, Lipparini, Polack, Stamm, Cances, Schnieders, Ren, Maday, Piquemal (2015) J Chem Theory Comput 11:2589. Scalable evaluation of polarization energy and associated forces in polarizable molecular dynamics : II.Towards massively parallel computations using smooth Particle Mesh Ewald. Shi, Ren, Schnieders, Piquemal (2015) Reviews Comp Chem 28, 51-84. Polarizable force fields for biomolecular modeling. Lagardère, Jolly, Lipparini, Aviat, Stamm, Jing, Harger, Torabifard, Cisneros, Schnieders, Gresh, Maday, Ren, Ponder, Piquemal (2018) Chem. Sci. 9, 956-972. Tinker-HP : a Massively Parallel Molecular Dynamics Package for Multiscale Simulations of Large Complex Systems with Advanced Polarizable Force Fields. Simonson, Archontis, Karplus (2002) Accts Chem Res 35:430. Free energy simulations come of age. Simonson (2016) The physical basis of ligand binding. Chapter one (pages 3-44), In Silico Drug Discovery and Design : Theory, Methods, Challenges, and Applications, CRC Press, Editor C. Casavotto