Prof. F.L. Gervasio Research Group

The Arch from the Stones: Understanding Protein Folding Energy Landscapes via Bioinspired Collective Variables Protein folding remains a formidable challenge despite significant advances, particularly in sequence-to-structure prediction. Accurately capturing thermodynamics and intermediates via simulations dem...

How do proteins really fold? Our latest @pubs.acs.org JPCL paper with @saureli.bsky.social @valeriorizzi.bsky.social @mheritier.bsky.social unveils a new MD strategy to investigate it in atomistic resolution by focusing on water and side-chain interactions. check it out pubs.acs.org/doi/10.1021/...

Enhanced Sampling and Tailored Collective Variables Yield Reproducible Free Energy Landscapes of Beta-1 Adrenergic Receptor Activation The beta-1 adrenergic receptor (ADRB1) is a critical target for cardiovascular drugs, yet our understanding of how it is activated remains incomplete. Capturing the concerted interplay of agonists, solvent, ions, and protein microswitches is a significant challenge for conventional simulation methods and is essential for unraveling this process. Here, we address this challenge by implementing a powerful enhanced sampling framework that integrates the OneOPES enhanced sampling algorithm with a set of biologically motivated collective variables (CVs). These CVs are designed to track several key features of the activation process simultaneously, including rearrangement of conserved microswitches, the state of the sodium ion binding pocket, and dynamics of critical water molecules. Using this framework, we mapped the multidimensional free energy landscapes of the ADRB1 receptor in both its apo- and adrenaline-bound holo states. Our analysis reveals a detailed, stepwise activation pathway that quantifies the known modulatory roles of sodium ions and protonation states and identifies essential water-mediated networks that stabilize the active conformation. This work provides a detailed overview of ADRB1 activation and establishes the robustness of our OneOPES approach for investigating complex activation mechanisms with the potential for application to other Class A GPCRs.

New in @pubs.acs.org JCTC: We've mapped the complete activation pathway of the β1-adrenergic receptor using our OneOPES enhanced sampling method and tailored CVs. Our approach reveals how sodium ions, water networks & protein microswitches work together. pubs.acs.org/doi/full/10.... #GPCR

Happy to share the latest work from the lab, led by @mudgal17.bsky.social‬, in collaboration with the Weis lab @ethzurich.bsky.social.
How do nuclear membranes fuse during NPC assembly? We answer this question in our latest work, where we identify a new mechanism for membrane fusion… (1/13)

No, AlphaFold has not completely solved protein folding Biology is hard. Yes, even for AI.

AlphaFold is great, but contrary to public opinion it has not completely solved the protein folding problem. Much work remains to be done.
clauswilke.substack.com/p/no-alphafo...

Can the US afford to lose its 1.1 million international students? International students contributed $43.8bn to the US economy last year and created 378,175 jobs nationwide.

“the 1.1 million international students studying in the US contributed $43.8bn to the US economy during the 2023–2024 academic year, creating 378,175 jobs nationwide.”

www.aljazeera.com/news/2025/6/...

Great to see our collaborative work featured by @irbbarcelona.org!

➡️ Read more here: bit.ly/42LlJm9

📑 Read the full article: rdcu.be/ef6YX
📝 Support our statement: bit.ly/3zVS3qm

#MDDB #FAIRdata #OpenScience #MolecularDynamics

On the design space between molecular mechanics and machine learning force fields A force field as accurate as quantum mechanics (QMs) and as fast as molecular mechanics (MMs), with which one can simulate a biomolecular system efficiently eno

Force fields with QM accuracy and MM speed are the theoretical biophysicist's Philosopher's Stone. I used ANIX2 with OpenFF and OpenMM. The results were insightful but at the expense of huge computational costs. #MLFF #biophysics #moleculardynamics

Andrew Chen, co-founder of one of my favorite denim brands, 3sixteen, breaks down how the tariffs affect his company

IG 3sixteen

Decentralized databases in biomedical research: lessons from recent events: The recent shutdown of critical health databases by the US CDC is a wake-up call for the research community about the vulnerability of centralised databases: EMBO reports: Vol 0, No 0 EMBO Press is an editorially independent publishing platform for the development of EMBO scientific publications.

…and @alfonsovalencia.bsky.social advocates in @emboreports.org for a distributed biomedical database infrastructure based on the imperiled yet utterly essential CDC resources www.embopress.org/doi/10.1038/...

Very proud of our new review article on the Beta 1-Adrenergic GPCR now available on bioRxiv: www.biorxiv.org/content/10.1....
With @saureli.bsky.social @valeriorizzi.bsky.social and Nicola we used OneOPES to fully converge the free energy landscapes associated with B1AR apo/holo activation.

EMBL has a single PhD application where a student can apply to any of our 80 labs in our 6 sites, with applications twice a year--the next March 10th! No need for MS, no application fee. Ranked 13th in the world on basis of publications, with emphais on junior faculty

www.embl.org/about/info/e...

How Trump 2.0 is reshaping science Since US President Donald Trump took office in January 2025, his team has made major changes to the federal government that have disrupted research and ...

Since US President Donald Trump took office last month, his team has made major changes that have disrupted research and research institutions in the US and beyond. Follow our coverage of the Trump administration's impact on science around the world:

https://go.nature.com/3QGKmJu

Awesome paper!
BioEmu from MSR: Scalable emulation of protein equilibrium ensembles with generative deep learning www.biorxiv.org/content/10.1...

Looking forward to hearing more explanainers in tomorrow's reading group session on zoom at 9am PT / 12pm ET / 6pm CET: portal.valencelabs.com/logg

Our new review article on "Computational advances in discovering cryptic pockets for drug discovery" is now available on COSB doi.org/10.1016/j.sb...
In collaboration with Pande's lab at JnJ and Cournia's lab at BRFAA we reviewed the state of the art in silico tools for studying cryptic pockets.

We are searching for a Research Assistant/Bioinformatician at @irbbarcelona.org

bbglab.irbbarcelona.org/2024/12/job-...

#IRBJobs

😂

AlphaFold3 versus experimental structures: assessment of the accuracy in ligand-bound G protein-coupled receptors - PubMed G protein-coupled receptors (GPCRs) are critical drug targets involved in numerous physiological processes, yet many of their structures remain unresolved due to inherent flexibility and diverse ligan...

pubmed.ncbi.nlm.nih.gov/39643640/ “while AlphaFold3 shows improved performance over AlphaFold2 in predicting overall GPCR backbone architecture, significant discrepancies persist in ligand-binding poses, particularly for ions, peptides, and proteins.”

Super excited to preprint our work on developing a Biomolecular Emulator (BioEmu): Scalable emulation of protein equilibrium ensembles with generative deep learning from @msftresearch.bsky.social ch AI for Science.

www.biorxiv.org/content/10.1...

I'm excited to share a new manuscript with Jiaqi Zhu characterizing the conformational ensembles of covalent adducts formed by a disordered protein and small molecule drugs:
biorxiv.org/content/10.1...

Code + Ensembles:
github.com/paulrobustel...

PLUMED Tutorials: a collaborative, community-driven learning ecosystem In computational physics, chemistry, and biology, the implementation of new techniques in a shared and open source software lowers barriers to entry and promotes rapid scientific progress. However, ef...

📢 New #preprint describing our community effort to share #plumed tutorials arxiv.org/abs/2412.03595 ! Explore the tutorials at www.plumed-tutorials.org

Do you want to work at the interface of molecular simulations, structural biology experiments and #AI? Come to Paris for a PhD at @pasteur.fr 1 PhD position is available in our lab funded by ERC_Research. Please repost!! #compchem #compbio Info 👇 research.pasteur.fr/b/15Hr

Nice work!

Jobs -

Hello! I'm posting this both here and on the X-rated site, let's see where it gets more re-posts 😇. We are looking for a research software engineer to help us develop (even) better code for #compchem #atomicscale #machinelearning. Check out the specs and apply!
www.epfl.ch/labs/cosmo/i...

Very excited to present the structural and mechanistic basis for stress response silencing by the monster E3 ligase SIFI.

www.biorxiv.org/content/10.1...

Conclusions of assessment of 3D category

Assessors’ conclusions of the 3D category (individual protein chains) of #CASP16 🧪

Conclusion slide of oligomer prediction assessment

#CASP16 assessors’ summary of the protein complex category 🧪 🧬

Figure from the preprint "A coarse-grained model of disordered RNA for simulations of biomolecular condensates" showing re-entrant phase separation of MED1-IDR and a disordered RNA, and partitioning of IDRs from HP1a and SPT6.

While the preprint is sitting in a thanksgiving queue at bioRxiv, let me just give you a teaser for RNA-CALVADOS in work led by Ikki Yasuda

Investigating Ligand-Mediated Conformational Dynamics of Pre-miR21: A Machine-Learning-Aided Enhanced Sampling Study MicroRNAs (miRs) are short, noncoding RNA strands that regulate the activity of mRNAs by affecting the repression of protein translation, and their dysregulation has been implicated in several patholo...

Our latest @acspublications.bsky.social JCIM study unveils new insights into pre-miR21 conformational dynamics using innovative computational techniques. Potential game-changer for RNA processing inhibition.
#MicroRNA #ComputationalChemistry #DrugDiscovery
pubs.acs.org/doi/10.1021/...

Good to have you here! I also recently moved here. Have you tried Sky Follower Bridge? It can help rebuild the network.

Our first #openreview has been published! disq.us/t/4r5064p Olivier Languin-Cattoën and
@bussigio.bsky.social reviewed a #preprint by Guillaume Stirnemann and Glen Hocky on catch bonding behavior in vinculin-actin unbinding kinetics