Sanim Rahman

Postdoctoral Fellow at Penn (Greenberg Lab) | JHU ‘25 (Wolberger Lab) | USF '19 (Varma Lab) |

[Sanim Rahman @SanimRahman4]

I am thrilled to share the main product of my PhD! Let's roll out an interesting story on the H2AK119 DUB USP21 where cryo-EM, in silico PPI screening, and AF3 modeling reveal a novel mode of DUB activity and regulation... https://t.co/3mBfDpdO1b (1/8)

[Sanim Rahman @SanimRahman4]

@RogerRogergr @CWolberger Thank you Roger!!!

[Sanim Rahman @SanimRahman4]

I am pleased to share the final piece of work from my time in the Wolberger Lab. Led by undergraduate Yash Bhargava, we performed a benchmark of AF3 on nucleosome-containing structures. Thank you to @CWolberger for allowing me to build this project up!

https://t.co/BOtP5cU33P

[Sanim Rahman @SanimRahman4]

ChatGPT couldn't have picked a better 2025 summary than this

[Sanim Rahman @SanimRahman4]

Excited to share that my work on USP21 is now published in @ScienceAdvances! A huge thank you to @CWolberger @HicksChadW and Alex Gwizdala who helped with this work.

https://t.co/2x6hxpfjq5

[Sanim Rahman @SanimRahman4]

Looking forward to presenting my forthcoming work in part of the Fragile Nucleosome seminar series this Wednesday. If you are interested in chromatin, ubiquitin, and/or structural biology register below! https://t.co/lQfSZw2bZ6

[Martin Pacesa @MartinPacesa]

Exciting to see our protein binder design pipeline BindCraft published in its final form in @Nature ! This has been an amazing collaborative effort with Lennart, @csche11h, @sokrypton, @befcorreia and many other amazing lab members and collaborators.

https://t.co/PTMoqQqwcU

[Roger Greenberg @RogerRogergr]

Please see our review article in NSMB, “Mechanisms and genomic implications of BIR”. Adel Atari and @HaoyangJiang2 focus on mammalian BIR, its relationships to human disease, and genome engineering. Thanks to reviewers for helpful comments.

https://t.co/RHa74TmS2F

[Stephen Fried JHU @fried_lab]

Very pleased to share a recent @fried_lab publication, in which we show how an #IDR modulates the substrate specificity of a yeast histone deubiquitinase, Ubp10. 1/5 #FriedLabNews
https://t.co/yNsRHPXAp4

[Gabriele Corso @GabriCorso]

📢 Call for proposals: Boltz small-molecule design collaboration! 🧬
Can we help design your ideal molecule? Can you help us improve our open-source models? Please reach out or share with scientists you know! More details below!

It has been great to see the level of excitement around our Boltz-2 release. Along with the structure and affinity model, we are working on new workflows for hit-discovery and hit-to-lead of small molecules. We have seen very strong computational results and we are now interested in validating them across a range of different targets and real-world settings.

Do you have a target on which you would like to design or optimize small-molecule binders? Do you have an associated chemical or functional assay that you can run to validate the designs? If the answer is yes to both questions, we would love to hear from you and collaborate.

As part of these collaborations, we would work alongside you to tailor our workflows for your task, run the large scale design on our cluster, and return to you the designed molecules alongside their expected scores. We ask you to commit to testing the top (according to your judgement) designed compounds and send us back the experimental results within 2 months of the selection.

You’ll have full IP of the compounds we send you and have the opportunity (not necessity) to be included alongside with the experiments you run in a joint journal publication. If this is something that might interest you, please reach out to me at gcorso at https://t.co/VkKWACM16p or DM me on the boltz-community Slack!

[Sanim Rahman @SanimRahman4]

@Bis_acrylamide Also, we are modeling the initial kinase-substrate interaction. Although short-lived (due to phospho rxn), these interactions are specific. AF-M can model interactions but in no way can we decouple binding kinetics or affinity during the rxn. We can discuss more via DM.

[Sanim Rahman @SanimRahman4]

I am thrilled to share the main product of my PhD! Let's roll out an interesting story on the H2AK119 DUB USP21 where cryo-EM, in silico PPI screening, and AF3 modeling reveal a novel mode of DUB activity and regulation... https://t.co/3mBfDpdO1b (1/8)

[Sanim Rahman @SanimRahman4]

@Bis_acrylamide Great question! This is a feature of AF-multimer that we and others in the field have noticed with in silico pulldowns. If a true interaction exists that AF-M can predict, it will score a high ipTM, indicating AF-M is confident in its prediction.

[Sanim Rahman @SanimRahman4]

A big thank you to @CWolberger for her incredible mentorship and support. Also, a huge thank you to my colleagues @MikeyXtalsPhd @HicksChadW and Alex Gwizdala for their contributions. (8/8)

[Sanim Rahman @SanimRahman4]

So, how is autoinhibition relieved? Using AlphaFold-Multimer, I performed an in silico PPI screen to search for USP21 IDR interactors. Amazingly, I find that my top hits, kinases and 14-3-3 proteins, are poised to interact with known IDR phosphorylation sites! (4/8)

[Sanim Rahman @SanimRahman4]

Many USP DUBs have long disordered regions. Analyzing all human USPs, I find that this mode of autoinhibition may be prevalent across some members of the USP family. Indeed, some of the DUBs I identified have been reported to be regulated by phosphorylation of their IDRs. (7/8)

[Sanim Rahman @SanimRahman4]

The structure revealed a unique binding mode that differs from both PR-DUB and USP16. Although this was cool to see, I had to ask, what is the other half of USP21 doing? Interestingly, I find that the IDR is an autoinhibitory module! (3/8)

[Sanim Rahman @SanimRahman4]

I resolved the structure of the catalytic domain of USP21 bound to an H2AK119ub nucleosome. Oddly, this was a difficult sample for cryo-EM, but commercial graphene oxide grids saved the day! (2/8)

[Sanim Rahman @SanimRahman4]

At this point, I don’t think anyone’s job is safe at HHS. What an insane move…

[WIRED @WIRED]

Dr. Richard Youle was among at least 10 principal investigators who were fired as part of Robert F. Kennedy Jr’s devastating reduction of federal employees working in public health.