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A part of my PhD work is now out in @Nature.
We address one of the biggest open questions in GPCR biology — the structural basis of ligand efficacy.
Using naloxone (Narcan) and loperamide, we capture GDP-bound MOR–Gi intermediates, visualize nucleotide release, and derive a comprehensive model of how these drugs modulate signaling:
🔗 nature.com/articles/s41586-0…
Saif Khan retweeted
Structural basis of stepwise G protein activation by a viral chemokine receptor biorxiv.org/content/10.64898…
Saif Khan retweeted
…and here’s an excellent news feature on our recent @Nature paper on the μ-opioid receptor, written by first author Saif Khan @sfk_usc: theconversation.com/how-does…
Saif Khan retweeted
If there is big biotech announcement happening, #MolecularNodes is being used for it. I only had the realisation in the past day, but it's strange to have my software very quickly become the visual face for $100M announcements and massive scientific breakthroughs.
Saif Khan retweeted
Very interesting read! nature.com/articles/s41586-0…
Saif Khan retweeted
Trojan scientists are one step closer to designing safer painkillers. At @USCDornsife, biologists visualized how opioids engage brain receptors. dornsife.usc.edu/news/storie…
Saif Khan retweeted
Interesting how two similar tweets - different scales - disciplines - appear in sequence on a social media. Look at the video in the left post teapaw.org/CorneliusGati/status/1… Molecular machines moving on a backbone similar to the Mobile Servicing System movement on @Space_station #nanotechnology #genomics #astrobiology @CorneliusGati @NASAScience
Excited to share @Nature: How does naloxone (Narcan) stop an opioid overdose? We determined the first GDP-bound μ-opioid receptor–G protein (wt) structures and found naloxone traps a novel "latent” state, preventing GDP release and G protein activation. 🧵
nature.com/articles/s41586-0…
Saif Khan retweeted
A part of my PhD work is now out in @Nature.
We address one of the biggest open questions in GPCR biology — the structural basis of ligand efficacy.
Using naloxone (Narcan) and loperamide, we capture GDP-bound MOR–Gi intermediates, visualize nucleotide release, and derive a comprehensive model of how these drugs modulate signaling:
🔗 nature.com/articles/s41586-0…
Saif Khan retweeted
お、聞いていたやつだ。
””Structural snapshots capture nucleotide release at the μ-opioid receptor”
nature.com/articles/s41586-0…
Saif Khan retweeted
Supported by extensive molecular dynamics simulations, we assembled the first half of the G protein activation pathway — a major step toward understanding how GPCRs translate drug binding into cellular signaling. (7/n)
Saif Khan retweeted
The mind-blowing part: a “latent” state — where the receptor and G protein both appear inactive, yet remain bound to each other. Naloxone traps this state, stalling activation. This likely explains its ability to block opioid signaling so effectively. (6/n)
Saif Khan retweeted
Que belleza de animacion!
Excited to share @Nature: How does naloxone (Narcan) stop an opioid overdose? We determined the first GDP-bound μ-opioid receptor–G protein (wt) structures and found naloxone traps a novel "latent” state, preventing GDP release and G protein activation. 🧵
nature.com/articles/s41586-0…
Saif Khan retweeted
Excited to share @Nature: How does naloxone (Narcan) stop an opioid overdose? We determined the first GDP-bound μ-opioid receptor–G protein (wt) structures and found naloxone traps a novel "latent” state, preventing GDP release and G protein activation. 🧵
nature.com/articles/s41586-0…
The awesome Mohsen Ranjbar performed Molecular dynamics on these states, which tracked perfectly with the model we derived from experimental structures – GDP release follows a progressive loss of affinity driven by ligand-induced allosteric transitions across MOR–Gi. Efficacious ligands (e.g. loperamide) promote these transitions, while weaker ones (e.g. naloxone) stall them, precluding GDP release and Gi activation. Thus, addressing decades of debate on the structural and functional mechanisms of GDP in G-protein signaling.
You can read all this and more in our paper that is out now in @Nature. I am deeply grateful to all those who have helped bring this work to life. First and foremost, my PhD advisor, the incredible @CorneliusGati, who makes it all possible. All our incredible co-authors. Gye Won Han for helping me survive new states, new maps and new models, on the daily! And a most special thanks to blender-sensei Vishwang (WANG-3D) for helping me create some stunning 3D art-work!
Saif Khan retweeted
This year’s chemistry laureate Omar Yaghi was born in Amman, Jordan, in 1965 to parents who were refugees from Palestine. When we spoke to him he shared his story:
“I grew up in a very humble home, we were a dozen of us in one room, sharing it with the cattle that we used to raise. I was born in a family of refugees, and my parents could barely read or write. My father finished sixth grade and my mother couldn’t read or write. It’s quite a journey. Science allows you to do it. Science is the greatest equalising force in the world.
Smart people, talented people, skilled people exist everywhere. That’s why we really should focus on unleashing their potential through providing them with opportunity.”
Today Yaghi shared the 2025 Nobel Prize in Chemistry with Susumu Kitagawa and Richard Robson for their work developing metal–organic frameworks.
Learn more about the prize: nobelprize.org/prizes/chemis…
