Computational biophysicist specialized in GPCRs, beta3 integrins, and other membrane proteins. Professor and Dean at Icahn School of Medicine at Mount Sinai.
After the most surreal peer review process we are out in the wild with BOLD-GPCRs: A Transformer-Powered App for Predicting Ligand Bioactivity and Mutational Effects across Class A GPCRs | Journal of Chemical Information and Modeling
pubs.acs.org/doi/full/10....
BOLD-GPCRs: A Transformer-Powered App for Predicting Ligand Bioactivity and Mutational Effects across Class A GPCRs
G Protein-Coupled Receptors (GPCRs) are important targets for drug discovery owing to their ability to respond to a broad range of stimuli and their involvement in numerous pathologies. Although traditional ligand-based and structure-based approaches have facilitated the development of effective therapeutics for many GPCRs, these approaches often fall short when applied to receptors with limited ligand or structural data. This limitation highlights the critical need for advanced strategies capable of accurately predicting ligand bioactivity across the entire GPCR family, especially for understudied receptor subtypes. In this study, we introduce BOLD-GPCRs (BERT-Optimized Ligand Discovery for GPCRs), a deep learning framework designed to enhance the prediction of ligand bioactivity across class A GPCRs. Accessible via a user-friendly web interface, BOLD-GPCRs employs transfer learning and leverages curated data sets of known class A GPCR ligands, receptor sequences, and signaling-relevant mutations. By integrating dense neural network classifiers with transformer-based protein language models, BOLD-GPCRs captures complex relationships between receptor sequence/function and ligand activity. Our results demonstrate that BOLD-GPCRs achieves robust predictive performance for both ligand bioactivity and mutational effects across a broad range of class A GPCRs, underscoring its potential as a valuable tool for ligand discovery, especially for poorly characterized receptors.
Kicking off the new year with a completely refreshed look for the Filizola Lab website. Happy 2026, everyone!
www.filizolalab.orgOUT NOW! The Graduate School of Biomedical Sciences Dean's Report and message from Dean
@martafilizola.bsky.social. Learn about the Graduate School at Mount Sinai's growth, innovation and achievement, and how they have excelled in 2025 👉
reports.mountsinai.org/article/grad...It’s official: ChatGPT can't draw a GPCR, but you’ll master them in the Filizola Lab
😜 Join Us! (send your CV and the names of at least two references to my institutional email)
#Postdoc #scientist #researchOur new work with Daniel Wacker’s Lab: not only do structurally different PAMs of the mu
#opioid receptor bind at different sites but their modulatory mechanisms also differ as assessed by molecular
#dynamics and information theory validated by functional experiments
www.biorxiv.org/content/10.1...
Structural and dynamic studies uncover a distinct allosteric modulatory site at the mu-opioid receptor
Positive allosteric modulators (PAMs) of the μ opioid receptor (MOR) offer a promising path toward safer opioid therapeutics, yet their mechanisms of action remain poorly understood. Here, we uncover ...
For your summer reading, check out the latest from our lab:
www.biorxiv.org/content/10.1...BOLD-GPCRs: A Transformer-Powered App for Predicting Ligand Bioactivity and Mutational Effects Across Class A GPCRs
G protein-coupled receptors (GPCRs) are important targets for drug discovery owing to their ability to respond to a broad range of stimuli and their involvement in numerous pathologies. Although tradi...
Join an ever-inquisitive community of scholars who make strategic and meaningful connections between science, medicine, education, and health care delivery. We look forward to welcoming new Master’s classes in Biomedical Sciences and Data Science and AI
youtu.be/NPNm4KOfwco
Graduate School of Biomedical Sciences – Master’s Programs
YouTube video by Icahn School of Medicine
It’s time to vote! If you give me your vote, I promise I will work hard and loud for you, the BPS community, and for science. Read my statement.
www.biophysics.org/elections/bp...
BPS Elections | Biophysical Society
Twenty case studies showing theoretical predictions in chemistry that were later confirmed experimentally.
#CompChem 🧪
doi.org/10.1515/pac-...
When theory came first: a review of theoretical chemical predictions ahead of experiments
For decades, computational theoretical chemistry has provided critical insights into molecular behavior, often anticipating experimental discoveries. This review surveys twenty notable examples from t...
The US will not only suffer a brain drain… but will also lose its background brain gain from the rest of the world.
econ.trib.al/3hYAuUZ25 years ago, I came to Stanford on a J1 visa and worked so hard to be worthy of that privilege. Today, I lead Immunology at Mount Sinai and I am the one who feel privileged when brilliant international trainees chose to join us.
“America First” Will Destroy U.S. Science
The U.S. government has sought to restrict immigration under the “America First” doctrine.
These policies severely harm American science by stripping it of talent and eliminating
a major driver of its...
New Notice on No Cost Extensions (or lack thereof)
grants.nih.gov/grants/guide...NOT-OD-25-110: Updated NIH Processes for No-Cost Extensions
NIH Funding Opportunities and Notices in the NIH Guide for Grants and Contracts: Updated NIH Processes for No-Cost Extensions NOT-OD-25-110. NIH
New insights from our group into how frogs resist toxic environments published today! 🎉🐸
Congratulations to Sandra, Samantha
@samnscience.bsky.social, Zhou, and our collaborators Tod Leighfield, Filizola lab
@martafilizola.bsky.social, and Du Bois lab at Stanford.
www.nature.com/articles/s41...
Structural basis for saxitoxin congener binding and neutralization by anuran saxiphilins
Nature Communications - Dinoflagellates and cyanobacteria produce saxitoxin (STX) congeners that block voltage-gated sodium channels. Here authors show how amphibians may sequester STX congeners...
Published an op-ed for
@cnn.com: “Nobel laureate: I owe America my success. Today, its scientific future is in danger.”
A personal reflection on what’s at stake as science funding gets slashed. I’d be grateful if you could amplify both in and beyond the science world.
www.cnn.com/2025/04/09/h...
Nobel laureate: I owe America my success. Today, its scientific future is in danger | CNN
Dr. Ardem Patapoutian says he watches “with deep sadness as the United States’ remarkable scientific enterprise, which took generations of hard work and national investment to build, faces a concerted...
Filizola lab - Gmeiner lab finally revealed
onlinelibrary.wiley.com/doi/abs/10.1...
Synthesis and Characterization of Photoswitchable Covalent Ligands for the β2‐Adrenoceptor
The β2-adrenergic receptor (β2AR) is a critical target for the treatment of airway diseases such as asthma or chronic obstructive pulmonary disease (COPD). To better understand its mechanism of actio...
"It’s kind of a textbook case of arbitrary and capricious.” A lawsuit alleges that NIH didn't follow proper procedure and was unconstitutionally vague when abruptly terminating >600 grants. My story
@science.org www.science.org/content/arti...
Lawsuit aims to overturn many NIH grant terminations
Multiple groups and NIH-funded scientists challenge agency’s decision as arbitrary and capricious
U.S. health agency purge includes 10 lab heads at National Institute of Neurological Disorders and Stroke
The reasons for selecting these researchers—who have led work on neuronal migration, dopamine receptors in neuronal signaling and the structure of ion channels, among other areas—remain unclear.
Why AI won’t replace scientists capable of making disruptive conceptual breakthroughs - they pose questions that challenge, rather than align with, the training data set
thomwolf.io/blog/scienti...🔭 The Einstein AI model
I shared a controversial take the other day at an event and I decided to write it down in a longer format: I’m afraid AI won't give us a compressed 21st century.
Are you aiming for leadership roles in pharmaceutical, biotech, high tech, or medical device companies? Consider applying to the revamped MSBS program @GradSchoolSinai @IcahnMountSinai, featuring 1 or 2-year tracks and non-thesis options tailored for industry professionals
At @GradSchoolSinai @IcahnMountSinai, we are excited to train the next generation of
#datascience and
#AI #professionals for
#PrecisionMedicine @MountSinaiNYC
and beyond. Apply here:
icahn.mssm.edu/education/ad...You got 5 min to really understand the real costs of scientific research - check out this video
www.youtube.com/watch?v=GzNc...
Understanding the Real Costs of Research
YouTube video by AAMCtoday
New picture for the Filizola lab on the relentless quest for breakthrough science to build a brighter future. Bring it on!
FRESH OFF THE PRESS
@filizolalab1 : Fine-Tuned Deep Transfer Learning Models for Large Screenings of Safer Drugs Targeting Class A GPCRs | Biochemistry
pubs.acs.org/doi/full/10....
Fine-Tuned Deep Transfer Learning Models for Large Screenings of Safer Drugs Targeting Class A GPCRs
G protein-coupled receptors (GPCRs) remain a focal point of research due to their critical roles in cell signaling and their prominence as drug targets. However, directly linking drug efficacy to the ...
Large crowd in New York City at Stand Up for Science.
Large scale investigation of GPCR molecular dynamics data uncovers allosteric sites and lateral gateways - Nature Communications
GPCR dynamics are critical for signal transmission into the cell. Here, the authors probe receptor plasticity using molecular dynamics simulations, enabling the detection of allosteric sites and drug ...
Francis Collins Retires From N.I.H.
www.nytimes.com/2025/03/01/u...
Francis Collins Retires From N.I.H., Saying Colleagues ‘Deserve the Utmost Respect’
Dr. Collins, a renowned geneticist, ran the National Institutes of Health for 12 years. His parting statement offered a pointed, if veiled, message to the Trump administration.
Francis Collins, the NIH Director for 12 years, led the Human Genome Project and other NIH efforts for 32 years, resigned today. Key words from his resignation letter
www.nytimes.com/2025/03/01/u...NIH ban on renewing senior scientists adds to assaults on its in-house research | Science | AAAS
www.science.org/content/arti...
NIH ban on renewing senior scientists adds to assaults on its in-house research
Policy follows firings of tenure-track scientists and suspension of training programs
Federal judge extends restraining order on Trump administration's cap on NIH indirect costs
Judge Angel Kelley kept in place an order blocking the Trump administration from implementing a 15% cap on NIH indirect cost payments
Well said
@dereklowe.bsky.social. Academia produces two vital products: (1) knowledge, and (2) human capital that knows how to use it. If we can’t train enough young creative US scientists to fulfill biopharma industry needs…
“I think they're being short-sighted, because fear does that to you.”
Biopharma companies and CEOs are keeping their heads down at their own peril. They should speak up about what’s happening to the NIH and other science agencies before it’s too late.
Silence gives consent. And no one should consent to this.
Make sure you, your trainees, and anyone else who might listen to you understands what "indirects" actually are, how they are established, and what Universities contribute. H/T
@rodallab.bsky.social
Please share widely!
www.youtube.com/watch?v=yxTD...
Facilities and Administrative (F&A) Costs Explainer
YouTube video by Association of American Universities
Red-state universities push back against NIH funding cuts
Red-state universities push back against NIH funding cuts
An administration official couldn’t explain why the 15 percent cap was chosen.
Statement of Association of American Universities, Association of Public & Land-grant Universities, and American Council on Education Regarding Their Legal Challenge to the Administration’s Cut to Lif...
AAU, ACE, and APLU have jointly filed suit in U.S. District Court in Massachusetts, along with a number of impacted research university co-plaintiffs, seeking to halt the NIH's proposed cut to life-sa...
🧵 The Fight Has Come to Them: Science, Institutions & The Indirects Cut
I want to take a moment to talk about the perspective behind these slides I put together. I’ve framed them to be as nonpartisan as possible—but in a moment this polarized, there are limits here. 1/
Made some slides for scientists to talk about what's been happening & what we should do next. There are probably many people better qualified than me to talk about these issues. If that's you, please, please, please consider holding some virtual advocacy training sessions for researchers this week.
The War on Science (Feb 2025 teach-in draft)
The War on Science What’s happening? What can we do about it? An interactive teach-in for biomedical researchers Please share, modify, and repurpose this template presentation (with credit). Good luck...
Since there has been a lot of misinformation circulating since last night, I find this AAMC infographic helpful in illustrating which types of expenses are and are not covered by NIH indirect cost reimbursements.
Another assault on US competitiveness at a time when biomedicine is roaring with innovation, an own-goal in a high-stakes international tournament. Of course the real losers are American people needing medicines and cures.
www.washingtonpost.com/health/2025/...
NIH cuts billions of dollars in biomedical funding, effective immediately
The move halts a large slice of money for most universities and research institutions virtually overnight, imperiling vital research in everything from cancer to heart disease.
The Howard Hughes Medical Institute, the nation’s largest private funder of biomedical research, yesterday killed a $60 million program aimed at making universities’ STEM education more inclusive.
scim.ag/3EtS0US
HHMI kills program aimed at boosting inclusivity in STEM education
“Inclusive excellence” program had committed $60 million to 104 institutions
15%.
In 2018, 10% was tried, but it was blocked by Congress.
www.nytimes.com/2017/09/11/u...
www.science.org/content/arti...
NIH plan to reduce overhead payments draws fire
White House wants to reduce indirect payments from 28% to 10%
Excellent 🧵 on this evening's NIH announcement of a dramatic reduction in indirect rates for research institutions, which amounts to a generational restructuring of the US research and development ecosystem. These cuts are effective immediately, not just for new grants but for existing ones.
6. The policy does not just affect funding going forward. All existing NIH grants will have their indirect rates cut to 15% as of today, the date of issuance.
For a large university, this creates a sudden and catastrophic shortfall of hundreds of millions of dollars against already budgeted funds.
[This post could not be retrieved]
Don't dismantle US scientific leadership in biomedical research
Text SIGN PMCFNT to 50409 to send this to your officials.
Health Resources Vanish Following D.E.I. and Gender Orders (Gift Article)
Vague federal directives have led to frantic action, and perhaps overreaction, before a Friday deadline.
Who can blame her?
Live Updates: Trump Administration Rescinds Freeze on Federal Grants and Loans
States Will Sue Trump to Stop Federal Grant Freeze
www.nytimes.com/2025/01/28/u...
States Plan to Sue to Block Trump’s Federal Grants Freeze
Democratic attorneys general from states including New York, California, Illinois, New Jersey, Rhode Island and Massachusetts are moving to keep funds flowing to state governments and cities.
All Democrats in Congress and the Senate will fight this—it’s illegal. But Republican lawmakers NEED to hear from their constituents! Priority order: call, then email. Be clear about how this will hurt education, the economy, and health! 🧪
www.nytimes.com/live/2025/01...
White House Orders Pause in All Federal Grants and Loans
All federal grants and loan disbursement paused by White House | CNN Politics
The White House budget office has ordered a pause on all federal grants and loans, according to an internal memorandum sent Monday.
Postdoc publications and citations link to academic retention and faculty success | PNAS
Postdoctoral training is a career stage often described as a demanding and anxiety-laden
time when many promising PhDs see their academic dreams sl...
“The impact of the collective executive orders and directives appears devastating.”
scim.ag/40ureTO
Trump hits NIH with ‘devastating’ freezes on meetings, travel, communications, and hiring
Researchers facing
Charged peptides instead of phospholipids? Another multidisciplinary study - a collaboration led by Neal Devaraj at UCSD. Sims done in my lab by
@conradopedebos.bsky.social
Out now in Angew Chemie
onlinelibrary.wiley.com/doi/10.1002/...
Diacylation of Peptides Enables the Construction of Functional Vesicles for Drug‐Carrying Liposomes
Membrane-forming phospholipids are generated in cells by enzymatic diacylation of non-amphiphilic polar head groups. Analogous non-enzymatic processes may have been relevant at the origin of life and....
So seems like the group is on a roll this month!
Here’s our latest work on parametrising coarse-grained models of sugars (disaccharides) by Astrid Brandner & in collaboration with Iain Smith,
@pauloctsouza.bsky.social and
@cg-martini.bsky.social pubs.acs.org/doi/10.1021/... #glycotime
Systematic Approach to Parametrization of Disaccharides for the Martini 3 Coarse-Grained Force Field
Sugars are ubiquitous in biology; they occur in all kingdoms of life. Despite their prevalence, they have often been somewhat neglected in studies of structure–dynamics–function relationships of macro...
Just one month to go until the 2025 GRS/GRC in Molecular Pharmacology! Get ready for an extraordinary program packed with cutting-edge science and inspiring discussions. Full details here:
www.grc.org/molecular-ph...2025 Molecular Pharmacology Conference GRC
The 2025 Gordon Research Conference on Molecular Pharmacology will be held in Ventura, California. Apply today to reserve your spot.
The letter signed by >15,000 physicians re: RFK Jr
www.documentcloud.org/documents/25...Martin Karplus, professor of chemistry emeritus at Harvard University and professeur conventionné at the University of Strasbourg, died Dec. 28 at the age of 94.
cen.acs.org/people/obitu... #chemskyWould you like to discover low-efficacy ligands or biased ligands for GPCRs? Our fine-tuned deep learning models using transfer learning and protein language processing make it possible!
www.biorxiv.org/content/10.1...
Fine-Tuned Deep Transfer Learning Models for Large Screenings of Safer Drugs Targeting Class A G Protein-Coupled Receptors
G protein-coupled receptors (GPCRs) remain a focal point of research due to their critical roles in cell signaling and their prominence as drug targets. However, directly linking drug efficacy to rece...
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.”
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...
Reposting this as I am reading yet another paper that says method X works poorly for problem Y even when no-one ever claimed that X should be applied to Y
