Florent Hédin

Florent Hédin
Qubit Pharmaceuticals

PhD in Physical Chemistry
Senior HPC Engineer @ Qubit Pharmaceuticals

About

41
Publications
5,753
Reads
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137
Citations
Additional affiliations
November 2020 - present
Qubit Pharmaceuticals
Position
  • Engineer
December 2018 - October 2020
INRIA Paris
Position
  • Engineer
September 2017 - December 2017
University of California, Los Angeles
Position
  • Researcher
Description
  • "Complex High-Dimensional Energy Landscapes" Long program September 11 - December 15, 2017 http://www.ipam.ucla.edu/programs/long-programs/complex-high-dimensional-energy-landscapes/?tab=overview
Education
October 2011 - October 2016
University of Basel
Field of study
  • Physical Chemistry
September 2009 - September 2011
University of Strasbourg
Field of study
  • Chemo-informatics
September 2006 - June 2009

Publications

Publications (41)
Article
Full-text available
Metastability is one of the major encountered obstacle when performing long molecular dynamics simulations, and many methods were developed to address this challenge. The “Parallel Replica”(ParRep) dynamics is known for allowing to simulate very long trajectories of metastable Langevin dynamics in the materials science community, but it relies on a...
Article
Full-text available
Recent molecular dynamics (MD) simulations of human hemoglobin (Hb) give results in disagreement with experiment. Although it is known that the unliganded (T0) and liganded (R4) tetramers are stable in solution, the published MD simulations of T0 undergo a rapid quaternary transition to an R-like structure. We show that T0 is stable only when the p...
Preprint
Full-text available
Partial infinite swapping (PINS) is a powerful enhanced sampling method for complex systems. In the present work thermodynamic observables are determined from reweighting at the post-processing stage for folding of (Ala) 10 in implicit and explicit solvent and for Xenon migration in myoglobin. In every case free energy surfaces are determined using...
Article
Full-text available
We 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 c...
Cover Page
Full-text available
We report a fast-track computationally driven discovery of new SARS-CoV-2 main protease (Mpro) inhibitors whose potency ranges from mM for the 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 fre...
Preprint
Full-text available
We investigate the computational performance of hybrid high-order methods applied to flow simulations in extremely large discrete fracture networks (over one million of fractures). We study the choice of basis functions, the trade-off between increasing the polynomial order and refining the mesh, and how to take advantage of polygonal cells to redu...
Preprint
Full-text available
We 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 high nM 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 energ...
Chapter
Full-text available
We are interested in solving flow in large tridimensional Discrete Fracture Networks (DFN) with the hybrid high-order (HHO) method. The objectives of this paper are: (1) to demonstrate the benefit of using a high-order method for computing macroscopic quantities, like the equivalent permeability of fracture rocks; (2) to present the computational e...
Preprint
Full-text available
We are interested in solving flow in large trimensional Discrete Fracture Networks (DFN) with the hybrid high-order (HHO) method. The objectives of this paper are: (1) to demonstrate the benefit of using a high-order method for computing macroscopic quantities, like the equivalent permeability of fracture rocks; (2) to present the computational eff...
Article
Full-text available
We recently reported that molecular dynamics simulations for hemoglobin require a surprisingly large box size to stabilize the T(0) state relative to R(0), as observed in experiments (El Hage et al., 2018). Gapsys and de Groot have commented on this work but do not provide convincing evidence that the conclusions of El Hage et al., 2018 are incorre...
Presentation
This presentation covers the content of the gen.parRep article (DOI: 10.1016/j.cpc.2019.01.005) plus some work in progress on a larger protein ligand system. As it contains unpublished results, you are required to send a private message to Florent Hédin in order to request access.
Poster
Full-text available
Metastability is one of the major encountered obstacle when performing long molecular dynamics simulations, and many methods were developed to address this challenge. The "Parallel Replica" (ParRep) dynamics is known for allowing to simulate very long trajectories of metastable Langevin dynamics in the materials science community, but it relies on...
Preprint
Metastability is one of the major encountered obstacle when performing long molecular dynamics simulations, and many methods were developed to address this challenge. The "Parallel Replica"(ParRep) dynamics is known for allowing to simulate very long trajectories of metastable Langevin dynamics in the materials science community, but it relies on a...
Preprint
Full-text available
Metastability is one of the major encountered obstacle when performing long molecular dynamics simulations, and many methods were developed to address this challenge. The "Parallel Replica" (ParRep) dynamics is known for allowing to simulate very long trajectories of metastable Langevin dynamics in the materials science community, but it relies on...
Presentation
Full-text available
Presentation given during the PINT workshop 7th edition https://www.math.univ-paris13.fr/~japhet/PINT2018.htm First figure comes from : https://sinews.siam.org/Details-Page/the-2013-nobel-prize-in-chemistry-celebrates-computations-in-chemistry-and-biology-1 Third figure comes from : https://chem.libretexts.org/Bookshelves/Physical_and_Theoretica...
Conference Paper
Full-text available
This white paper was prepared by the participants of the fall 2017 long program Complex High-Dimensional Energy Landscapes. Recent advances in computational resources and the development of high-throughput frameworks enable the efficient sampling of complicated multivariate functions. This includes energy and electronic property landscapes of inor...
Thesis
Full-text available
In this PhD Thesis molecular systems off increasing size and complexity are investigated, using both standard sampling and advanced sampling methods. The implementation and validation of two of those rare events sampling methods is described, namely the SA-MC and PINS algorithm. The development and use of a toolkit for fitting force fields para...
Presentation
Full-text available
PhD defense presentation, University of Basel, 22.09.2016
Presentation
Full-text available
Presentation at HPC department of Universität Basel Florent Hédin
Code
This performs MC or SA-MC simulations of Lennard-Jones clusters, as described in article http://pubs.acs.org/doi/abs/10.1021/ct500529w It was used for generating the LJ clusters results in the above linked article
Technical Report
Full-text available
Studies and structural analysis revealed a gate-trapping mechanism for the uptake of O2 in truncated Haemoglobin. This gate involves the Ile15, Ile19, Leu102, and Ile115 residues. To further study the gate-trapping process, MD and MC simulations with O2 outside the protein but close to the gate are performed. O2 is constrained to remain around the...
Presentation
Full-text available
Seminar presentation at University of Basel : overview of the efficiency of MC sampling, and discussion on the main sources of errors.
Poster
Full-text available
Spatial averaging algorithm is an efficient MC method which can be applied to problems where important regions (e.g. transition states) of the energy landscape may be difficult to sample with a standard random walk method, such as Metropolis sampling. At the heart of the method is the realization that from the equilibrium density a related, modifie...
Poster
Full-text available
Truncated hemoglobin (trHbN) is a protein involved in NO dioxygenation by converting nitric oxide to harmless nitrates: Fe(II)O2 + NO → Fe+(III) + NO− 3 . The tunnel system of trHbN plays an important role in determining and controlling ligand entrance, migration, and rebinding. Previous umbrella sampling studies and structural analysis of channel...
Poster
Full-text available
Spatial averaging algorithm: It is an efficient MC method which can be applied to problems where important regions (e.g. transition states) of the energy landscape may be difficult to sample with a standard random walk method, such as Metropolis sampling. At the heart of the method is the realization that from the equilibrium density a related, mod...
Presentation
Full-text available
Basics of MC sampling in computational chemistry ; comparison of plain Metropolis MC and of Spatial Averaging MC sampling for alanine dipeptide and Villin headpiece.
Thesis
Full-text available
Spatial Averaging is a Monte Carlo method introducing a new family of probability densities improving the sampling efficiency of the rare-event problems, while conserving the statistical properties of the original distribution. After a theoretical overview concerning Monte Carlo Methods, the principles of Spatial Averaging are introduced. After thi...
Technical Report
Full-text available
Ce dossier combine une étude bibliographique ainsi que les résultats d’une étude pratique sur le thème du Neighborhood Behavior, et plus particulièrement sur la valeur statistique de l’un de ses critères d’évaluation, le critère d’Optimalité. Dans la première partie, le Neighborhood Behavior (NB) est présenté en détail : pour cela, il est égalemen...
Presentation
Full-text available
But : étudier la valeur statistique du critère d'optimalité du Neighborhood Behavior, appliqué à une base de données de réactions organiques sous forme de Graphes Condensés de Réaction (GCRs).

Network

Cited By

Projects

Projects (9)
Archived project
Neighborhood behavior : valeur statistique du critère d'optimalité Travail de Master 2, Université de Strasbourg
Archived project
The aim is to learn physicochemical properties of interest from simple structural representations, using deep neural networks: in particular I would like to investigate how much can be learned from molecular fingerprints generated by using the SMILES molecular representation. This project was initiated in 0ctober 2017 during the IPAM's long program "Complex High-Dimensional Energy Landscapes"