Jean-Philip Piquemal

Assessing Boltz-2 Performance for the Binding Classification of Docking Hits The recently released Boltz-2 cofolding model is generating high expectations by enabling both protein–ligand structure and binding affinity predictions. When applied to a recently described and chall...

#compchem #compchemsky #biosky
Good read: Assessing Boltz-2 Performance for the Binding Classification of Docking Hits pubs.acs.org/doi/10.1021/...

#compchem #compchemsky Our paper in J. Phys. Chem. Lett.: "Accelerating Molecular Dynamics Simulations with Foundation Neural Network Models using Multiple Time-Step and Distillation" made it to one of the covers! pubs.acs.org/doi/full/10....

Quantum computers will finally be useful: what’s behind the revolution A string of surprising advances suggests usable quantum computers could be here in a decade.

#quantumcomputing Good read: Quantum computers will finally be useful: what’s behind the revolution
www.nature.com/articles/d41...

🚀 Game-changing speed for drug discovery simulations without trading accuracy for Relative Binding Free Energy (RBFE) calculations.
Dual-LAO delivers 15–30× faster simulations while maintaining industry-leading accuracy (~0.5–0.6 kcal/mol). #compchem
t.co/dDLVqXKvZm

🚀First paper published!
We introduce DMTS, a multi-time-step method for ML force fields
✔️×4 speed-up
✔️Accuracy preserved
✔️Generalizable to any ML potential
📄Link: pubs.acs.org/doi/full/10....
The preprint: arxiv.org/abs/2510.06562
@jppiquem.bsky.social
#MolecularDynamics #MachineLearning

🤩 New year, new publication using the FeNNix-Bio1 foundation model !

🚀« Accelerating Molecular Dynamics Simulations with Foundation Neural Network Models using Multiple Time-Step and Distillation» published in the Journal of Physical Chemistry Letters
#compchemsky #biosky #machinelearning

Accelerating Molecular Dynamics Simulations with Foundation Neural Network Models Using Multiple Time Steps and Distillation We present a distilled multi-time-step (DMTS) strategy to accelerate molecular dynamics simulations using foundation neural network models. DMTS uses a dual-level neural network, where the target accurate potential is coupled to a simpler but faster model obtained via a distillation process. The 3.5 Å cutoff distilled model is sufficient to capture the fast-varying forces, i.e., mainly bonded interactions, from the accurate potential, allowing its use in a reversible reference system propagator algorithm (RESPA)-like formalism. The approach conserves accuracy, preserving both static and dynamic properties, while enabling us to evaluate the costly model only every 3 to 6 fs depending on the system. Consequently, large simulation speedups over standard 1 fs integration are observed: nearly 4-fold in homogeneous systems and 3-fold in large solvated proteins through leveraging active learning for enhanced stability. Such a strategy is applicable to any neural network potential and reduces the performance gap with classical force fields.

#compchem #machinelearning
1st of the year in J. Phys. Chem. Lett.: "Accelerating Molecular Dynamics Simulations with Foundation Neural Network Models using Multiple Time-Step and Distillation". pubs.acs.org/doi/full/10....
(see also the updated preprint: arxiv.org/abs/2510.06562)

Point of no returns: researchers are crossing a threshold in the fight for funding With so little money to go round, the costs of competing for grants can exceed what the grants are worth. When that happens, nobody wins.

Good read: www.nature.com/articles/d41...

Cheers to 2026! Happy new year everyone.

#hpc #supercomputing #machinelearning #compchem
New Grand Challenges @gencifrance.bsky.social report dedicated to the Jean Zay 4 machine at IDRIS. Our work on the FeNNix-Bio1 machine learning foundation model can be found on pages 22-25.
genci.fr/sites/defaul...

Fast Parametrization of Martini3 Models for Fragments and Small Molecules Coarse-grained molecular dynamics simulations, such as those performed with the recently parametrized Martini 3 force field, simplify molecular models and enable the study of larger systems over longer time scales. With this new implementation, Martini 3 allows more bead types and sizes, becoming more amenable to studying dynamical phenomena involving small molecules such as protein–ligand interactions and membrane permeation. However, while solutions existed to automatically model small molecules using the previous iteration of the Martini force field, there is no simple way to generate such molecules for Martini 3 yet. Here, we introduce Auto-MartiniM3, an advanced and updated version of the Auto-Martini program designed to automate the coarse-graining of small molecules to be used with the Martini 3 force field. We validated our approach by modeling 81 simple molecules from the Martini Database and comparing their structural and thermodynamic properties with those obtained from models designed by Martini experts. Additionally, we assessed the behavior of Auto-MartiniM3-generated models by calculating solute translocation and free energy across lipid bilayers. We also evaluated more complex molecules such as caffeine by testing its binding to the adenosine A2A receptor. Finally, our results from deploying Auto-MartiniM3 on a large data set of molecular fragments demonstrate that this program can become a tool of choice for fast, high-throughput creation of coarse-grained models of small molecules, offering a good balance between automation and accuracy. Auto-MartiniM3 source code is freely available at https://github.com/Martini-Force-Field-Initiative/Automartini_M3.

#compchem #compbio Good read: Fast Parametrization of Martini3 Models for Fragments and Small Molecules pubs.acs.org/doi/10.1021/...

Automated Machine Learning Pipeline: Large Language Models-Assisted Automated Data set Generation for Training Machine-Learned Interatomic Potentials Machine learning interatomic potentials (MLIPs) have become powerful tools to extend molecular simulations beyond the limits of quantum methods, offering near-quantum accuracy at much lower computatio...

#compchem Good read: Automated Machine Learning Pipeline: Large Language Models-Assisted Automated Data set Generation for Training Machine-Learned Interatomic Potentials pubs.acs.org/doi/10.1021/...

Merry Christmas!!!

#compchem #compbio Last preprint of the year: "Fast, systematic and robust relative binding free energies for simple and complex transformations : dual-LAO".
arxiv.org/abs/2512.17624
Great work by N. Ansari. @qubit-pharma.bsky.social .
Another nice collab with J. Hénin.

Wishing you happy holidays. See you in 2026!!! #compchem

Also, if you check the Github, FeNNol can also launch MACE, MACE-OFF and ANI simulations. Enjoy! #compchem

A Foundation Model for Accurate Atomistic Simulations in Drug Design While artificial intelligence has revolutionized the prediction of static protein structures, characterizing their dynamics and interactions with drug candidates remains a computational bottleneck. He...

You can also check the updated version of the preprint that includes a unified transformers architecture as well as the full computation of the Freesolv hydration free energies dataset etc... #compchem #compbio
doi.org/10.26434/che...

GitHub - FeNNol-tools/FeNNol-PMC: FeNNol Pretrained Models Collection FeNNol Pretrained Models Collection. Contribute to FeNNol-tools/FeNNol-PMC development by creating an account on GitHub.

💫 We just released the weights of the #FeNNixBio1 foundation machine learning model for drug design! 💫

Weights: github.com/FeNNol-tools...
FeNNol code: github.com/FeNNol-tools...
The models are distributed under the open source ASL license (non-commercial academic research). #compchem #compbio

A Foundation Model for Accurate Atomistic Simulations in Drug Design While artificial intelligence has revolutionized the prediction of static protein structures, characterizing their dynamics and interactions with drug candidates remains a computational bottleneck. He...

You can also check the updated version of the preprint that includes a unified transformers architecture as well as the full computation of the Freesolv hydration free energies dataset etc...
doi.org/10.26434/che...

"C'est un vrai cri d'alarme" : de Lille à Angers, des universités alertent sur leur situation financière L'an dernier, les présidents d'universités étaient déjà montés au créneau en décembre pour dénoncer les restrictions budgétaires demandées par le gouvernement, après déjà plusieurs années de sous-fina...

"C'est un vrai cri d'alarme" : de Lille à Angers, des universités alertent sur leur situation financière
www.franceinfo.fr/societe/educ...
@afp.com @franceinfo.fr

Congrats to Cesar Féniou who succesfully defended his PhD: "Quantum algorithms for first-principles quantum chemistry"
@qubit-pharma.bsky.social

#compchem #quantumcomputing

New paper in collaboration with Q-CTRL demonstrating the use of NISQ hardware for the water placement problem in drug design, up to 123 qubits on IBM's Heron QPU! #quantumcomputing #compchem #drugdesign

#compchem #quantumcomputing
I’m thrilled to share this new preprint: "Practical protein-pocket hydration-site prediction for drug discovery on a quantum computer".
👉Check it out: arxiv.org/abs/2512.08390

Great collab with D. Loco (@qubit-pharma.bsky.social ), K. Barkemeyer & A. Carvalho (Q-CTRL)

Optimal Framework Constructs Lie-Algebra Generator Pools, Enabling Efficient Variational Quantum Eigensolvers For Chemistry Researchers have developed a new mathematical strategy that efficiently identifies the essential building blocks of complex systems, dramatically improving computational power for applications ranging...

Quantum Zeitgeist @superposition.bsky.social highlighted our recent preprint: "An Optimal Framework for Constructing Lie-Algebra Generator Pools: Application to Variational Quantum Eigensolvers for Chemistry" #quantumcomputing #compchem
quantumzeitgeist.com/variational-...

The Schrödinger equation, together with the associated wave function often denoted by the Greek letter Ψ, is at the core of quantum mechanics. Over the past century, quantum mechanics has served as the foundation for modern physics theories, including quantum field theory. The theoretical groundwork is now being transformed into new disciplines, such as quantum information science and technology, and quantum materials.

Over the past century, quantum mechanics has served as the foundation for modern physics theories, including quantum field theory. The theoretical groundwork is now being transformed into new disciplines.

Learn more in a new special issue of Science: https://scim.ag/4oz1y2a

Ce lundi 8/12, je représenterai @qubit-pharma.bsky.social à la journée "𝐐𝐮𝐚𝐧𝐭𝐮𝐦 & 𝐈𝐧𝐭𝐞𝐥𝐥𝐢𝐠𝐞𝐧𝐜𝐞 𝐀𝐫𝐭𝐢𝐟𝐢𝐜𝐢𝐞𝐥𝐥𝐞 - 𝐕𝐞𝐫𝐬 𝐮𝐧𝐞 𝐜𝐨𝐧𝐯𝐞𝐫𝐠𝐞𝐧𝐜𝐞 𝐝𝐞𝐬 𝐫𝐮𝐩𝐭𝐮𝐫𝐞𝐬 𝐭𝐞𝐜𝐡𝐧𝐨𝐥𝐨𝐠𝐢𝐪𝐮𝐞𝐬 ?".
evenium.events/quantum-inte...

#quantumcomputing #AI #artificialintelligence #machinelearning

#quantumcomputing #compchem
New preprint! The presented mathematical framework is general & applicable well beyond chemistry in fields including quantum error correction, quantum control, quantum machine learning, and more universally wherever compact Pauli basis are required. Congrats to the team!

#compchem #compchemsky #quantumcomputing
New group preprint: "An Optimal Framework for Constructing Lie-Algebra Generator Pools: Application to Variational Quantum Eigensolvers for Chemistry."
👉Check it out: arxiv.org/abs/2511.22593
@piquemalgroup.bsky.social @qubit-pharma.bsky.social

Comparing Force Field Treatments in QM/MM Studies of the SARS-CoV-2 RNA-Dependent RNA Polymerase (RdRp) Mechanism Molecular simulations have been instrumental in elucidating the SARS-CoV-2 lifecycle, thereby supporting the design and development of antiviral therapies and diagnostic tools for COVID-19. Here, the molecular mechanism of the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp), a potential target for antiviral drugs to treat COVID-19, was explored based on QM/MM simulations with fixed-charge and polarizable force fields (cFF and pFF, respectively). The free energy perturbation (FEP) method allowed exploring the free energy landscape of the enzymatic reaction mechanism, addressing key questions about the initial deprotonation of the 3′-OH group of the terminal nucleotide before a nucleophilic attack on the incoming nucleotide takes place. Indeed, among the five mechanisms explored, the most favorable was identified as a three-step process. The first step consists of a proton transfer from the 3′-OH group of the terminal nucleotide to a hydroxide group coordinated with an Mg2+ ion. Subsequently, the O3′ atom nucleophilically attacks the Pα atom of the incoming ATP. Finally, a proton is transferred from the water molecule formed in the first step to the γ-phosphate group of the pyrophosphate leaving group, regenerating the Mg2+-coordinated hydroxide group. This mechanism was found to be exergonic, with the rate-determining step being the nucleophilic attack, having a free energy barrier of 15.2 kcal mol–1. Both cFF and pFF yield consistent energetic and geometrical descriptions of the full RdRp-catalyzed reaction. Noncovalent interaction (NCI) and electron localization function (ELF) analyses provide insights into the electronic evolution during the reaction, showing strong polarization on electronic basins associated with the reactive oxygens O3′ and O3α. Together, findings contribute to a deeper understanding of the RdRp mechanism, which could aid in the discovery of new antiviral inhibitors.

#compchem #compchemsky #biosky Good read: Comparing Force Field Treatments in QM/MM Studies of the SARS-CoV-2 RNA-Dependent RNA Polymerase (RdRp) Mechanism pubs.acs.org/doi/10.1021/...

Weighted Ensemble Simulations Reveal Novel Conformations and Modulator Effects in Hepatitis B Virus Capsid Assembly Molecular dynamics (MD) simulations provide a detailed description of biophysical processes, allowing mechanistic questions to be addressed at the atomic level. The promise of such approaches is partl...

#compchem #biosky #compchemsky Good read: Weighted Ensemble Simulations Reveal Novel Conformations and Modulator Effects in Hepatitis B Virus Capsid Assembly. pubs.acs.org/doi/10.1021/...