John Schneekloth (Jay)

Machine Learning‐Augmented Molecular Dynamics Simulations (MD) Reveal Insights Into the Disconnect Between Affinity and Activation of ZTP Riboswitch Ligands This study combines computational and experimental approaches to study how natural and synthetic small molecules interact with the ZTP riboswitch, a bacterial RNA element that regulates gene expressi....

Honored to see that our collaborative work with Pratyush Tiwary and Adrian Ferré-D'Amaré on the ZTP riboswitch was selected as a very important paper by @angewandtechemie.bsky.social! onlinelibrary.wiley.com/doi/10.1002/...

Hear-hear! Science making amazing progress and saving lives despite increasing barriers is something to be celebrated.

Congrats to the people who helped get this across the finish line - Mo Yang, Peri Prestwood, other co-authors, and collaborators Kevin Weeks and Adrian Ferre-D'Amare!

We also demonstrate for the first time that bonding interactions between ligands and K+ ions in G4s can exist. These new dyes have increased brightness and performance in imaging relative to TO and TO1-biotin (the dyes Mango II was evolved to bind).

Structure-informed design of an ultrabright RNA-activated fluorophore - Nature Chemistry Fluorogenic RNA aptamers such as Mango are powerful tools for RNA imaging. An ultrabright RNA-activated fluorophore with improved photophysical performance has now been developed using a structure-inf...

Out now in @natchem.nature.com! Lots to unpack here, but in short - we show that SMM enabled fragment based design is useful on RNAs to improve chemical properties like affinity and brightness of fluorophore ligands.

www.nature.com/articles/s41...

Machine learning‐augmented molecular dynamics simulations (MD) reveal insights into the disconnect between affinity and activation of ZTP riboswitch ligands The challenge of targeting RNA with small molecules necessitates a better understanding of RNA-ligand interaction mechanisms. However, the dynamic nature of nucleic acids, their ligand-induced stabil...

New work from the lab - With Pratyush Tiwary and Adrian Ferre-D'Amare, we study ligands that activate the ZTP riboswitch. Experimental and theoretical approaches show that ligand on rates influence activity by non-obvious mechanisms when targeting RNA!

onlinelibrary.wiley.com/doi/10.1002/...

Congratulations to Evan J. Burke, a grad student in the Krebs and Bollinger labs in Penn State's Department of Chemistry, on being named a 2025 #ACSBIOL Young Investigator!
@jmarbol21.bsky.social

Interventionally targeting somatic CAG expansions can be a rapid disease-modifying therapeutic avenue: Preclinical evidence. Huntington disease (HD) is caused by inherited CAG expansions, which continue expanding somatically in affected brain regions to hasten disease onset and progression. Therapeutically diminishing somat...

Another new piece of work from the lab - I played a small role in this really exciting work coming out of the Pearson lab at Sick Kids in Toronto dealing with preclinical studies on CAG repeat instability in Huntington disease. Check it out: www.biorxiv.org/content/10.1...

Harnessing Molecular Recognition for Small‐Molecule‐Mediated Reversible Photochemical Control Over mRNA Translation A small molecule ligand undergoes traceless, reversible photocrosslinking to PreQ1 RNA aptamer in a selective manner, dependent on both the RNA sequence/structure and ligand chemical structure. A cag...

Hey, check it out - new work from the lab! We report the design of design traceless, reversible small molecule photocrosslinking probes that can be used to photochemically control the translation of mRNAs just using molecular recognition! Congrats to all! onlinelibrary.wiley.com/doi/10.1002/...

Research Technician - Open Chemistry Primary Work Address: 19700 Helix Drive, Ashburn, VA, 20147 Current HHMI Employees, click here to apply via your Workday account. Summary: Open Chemistry is a collaborative research group whose missio...

We're looking for 1-2 enthusiastic early career chemists to join our Open Chemistry team at @hhmijanelia.bsky.social. Come help us create amazing dyes and share them with the world. Please share with the best recent/soon-to-be B.S. chemists you know! bit.ly/42w8C6N

I love doing this, especially for the gut check about how your biases and intuition for what will/won't work can be so wrong!

Great news: NIH postbac program is recruiting again! If your grad school plans were affected by program cutbacks or admissions freezes this year I highly encourage you to apply, this could be a perfect opportunity. Please repost.

www.training.nih.gov/research-tra...

New work from my awesome colleague @vidigaljoana.bsky.social!

"rare high energy conformations"

The final #ACSBIOL sessions of #ACSSpring2025 are tomorrow morning, Thursday the 27th:

📰 Current Topics in #Biochem and #ChemBio, Room 31A

👩‍🎓 Undergraduate and Graduate Research, Hal G/H Room 8

Be sure to check out these excellent presentations!

#ACSBIOL Sessions on Wednesday, 26th at #ACSSpring2025:

Morning, Room 31A:
🏆 Eli Lilly Award to @brianliau.bsky.social

Afternoon, Room 31A:
🏆 ACS Chemical Biology Young Investigator Award to @jeremybaskin.bsky.social

Evening, Hall B2/C:
📜 Poster Session, Current Topics

@pubs.acs.org

Congrats @rche54.bsky.social, nice work!

Chemical tools to define and manipulate interferon-inducible Ubl protease USP18 - Nature Communications USP18 is a multifunctional cysteine protease involved in IFN pathways. Here, the authors report chemical probes and chemoproteomics platforms that allow to detect and perturb USP18 activity in complex...

Check out this awesome paper from my colleague @eunayoo.bsky.social about activity-based probes for USP18! www.nature.com/articles/s41...

We often focus on publicizing our work to other scientists but it's just as important to have journalists communicate with non-scientists as well!

I am about to survive my 1047th week in medicinal chemistry. This editorial is a visit on memory lane. Yes, starting in MedChem initially looks very daunting. MedChems love abbreviations & specialist slang to scare off laymen. But overcoming these hurdles is so rewarding in many dimensions.

This is the largest RNA we have published on screening to date - over 350 nt in length! This highlights the power of SMMs to discover chemical inhibitors of large, highly complex RNAs. Additionally, mechanistic work shows the mechanism of inhibition to be allosteric! Congrats to all who contributed.

Use of a small molecule microarray screen to identify inhibitors of the catalytic RNA subunit of Methanobrevibacter smithii RNase P Abstract. Despite interest in developing therapeutics that leverage binding pockets in structured RNAs—whose dysregulation leads to diseases—such drug disc

What a week! Really proud to share this work with Venkat Gopalan and Damien Wilburn in Nucleic Acids Research. We show that our SMM platform can be used to identify allosteric chemical inhibitors of an archaeal RNase P, an ancient ribozyme. academic.oup.com/nar/advance-...

We hope that this type of approach will eventually have impacts in the study and prediction of large RNA structural ensembles - and perhaps ligand discovery!

Thrilled to see our work in @pnas.org this week! With Pratyush Tiwary, we show that "thermodynamic maps" can be used to infer and predict information about RNA 3D structural ensembles! Proud to have played a small role in this exciting work. www.pnas.org/doi/10.1073/...

This is deeply concerning!

Americans are now one-third less likely to die from cancer at the same ages as Americans in 1990

Bioorthogonal Cyclopropenones for Investigating RNA Structure RNA sequences encode structures that impact protein production and other cellular processes. Misfolded RNAs can also potentiate disease, but a complete picture is lacking. To establish more comprehens...

Really excited to see this work out! In collaboration with Prof. Jen Prescher, we showed that their cyclopropenone labeling strategy can be applied to structured RNA! Thrilled to work with this fantastic team of scientists. pubs.acs.org/doi/10.1021/...

One of the reasons Bluesky is seeing more engagement: other platforms have adopted the behaviour of de-prioritising external links (like, say, to research papers) due to Ad models.

See this: bsky.app/profile/alt...

Here links can be freely shared without being drowned out or de-emphasized

Analysis of genetic requirements and nutrient availability for Staphylococcus aureus growth in cystic fibrosis sputum Staphylococcus aureus is one of the most common pathogens isolated from the lungs of people with cystic fibrosis (CF), but little is known about its ability to colonize this niche. We performed a Tn-s...

🎉 Our grad student @katherinelegg.bsky.social is a co-author on a new preprint about the genetic requirements and nutrient needs for Staphylococcus aureus growth in cystic fibrosis sputum. Congrats to @gramnegativity.bsky.social and all involved! shorturl.at/yfZQA 🧬 #CysticFibrosis #Microbiology

Years after the idea and preliminary experiments, Claire Coupland's amazing structure of the endogenous vacuolar- or vesicular-ATPase in its NATIVE vesicle is now in bioRxiv "High resolution cryo-EM of V-ATPase in native synaptic vesicles"
www.biorxiv.org/content/10.1...