Probing the surface states in Bi2Se3 using the Shubnikov-de Haas effect

Shubnikov-de Haas (SdH) oscillations are observed in Bi2Se3 flakes with high carrier concentration and low bulk mobility. These oscillations probe the protected surface states and enable us to extract their carrier concentration, effective mass and Dingle temperature. The Fermi momentum obtained is in agreement with angle resolved photoemission spectroscopy (ARPES) measurements performed on crystals from the same batch. We study the behavior of the Berry phase as a function of magnetic field. The standard theoretical considerations fail to explain the observed behavior.Comment: 6 pages, 8 figures. Accepted to Physical Review

Computationally driven discovery of targeting SARS-CoV-2 Mpro inhibitors: from design to experimental validation

International audienceWe report a fast-track computationally-driven discovery of new SARS-CoV2 Main Protease (Mpro) inhibitors whose potency range from mM for initial non-covalent ligands to sub-μM for the final covalent compound (IC50=830 +/- 50 nM). The project extensively relied on high-resolution all-atom molecular dynamics simulations and absolute binding free energy calculations performed using the polarizable AMOEBA force field. The study is complemented by extensive adaptive sampling simulations that are used to rationalize the different ligands binding poses through the explicit reconstruction of the ligand-protein conformation spaces. Machine Learning predictions are also performed to predict selected compound properties. While simulations extensively use High Performance Computing to strongly reduce time-to-solution, they were systematically coupled to Nuclear Magnetic Resonance experiments to drive synthesis and to in vitro characterization of compounds. Such study highlights the power of in silico strategies that rely on structure-based approaches for drug design and allows to address the protein conformational multiplicity problem. The proposed fluorinated tetrahydroquinolines open routes for further optimization of Mpro inhibitors towards low nM affinities