Shozeb

All details in Wilkins obituary by Prof Struther Anott. Must read. royalsocietypublishing.org/doi/pdf/10.1...

Franklin and Wilkins were not building molecular models of DNA at all. That was being done by WC. And Wilkins already had a diffraction pattern of A DNA long before Franklin came to KCL.

How I wish Prof Struther Arnott was alive to tell the story about the DNA structure saga. He was privy to the drama played out. It was Randall who pushed Franklin out of KCL taking DNA research away from her. Franklin herself showed a low res image in a seminar to Watson.

Affinity-selected peptide ligands specifically bind i-motif DNA and modulate c-Myc gene expression Abstract. c-Myc is an oncogene that is dysregulated in ∼70% of cancers. Its multifaceted function complicates effective drug targeting of the protein. i-Mo

Dr Chris Morris and I have a new paper in Nucleic Acids Research.

This paper has been a long time in the making & was affected by COVID so we are proud to have it published!

@shozebhaider.bsky.social
@effrosynialexandr.bsky.social
@chriswaudby.bsky.social

academic.oup.com/nar/article/...

Oh! New York and New Yorkers, you are stellar.

FormatMyPaper - The End of Manuscript Formatting Paste your paper, choose your journal, and let our AI handle the tedious rest. Get back to the science.

Need to try this in my next rejection

formatmypaper.com

A structure-based drug design conference at an impressive venue but more so with fantastic friends @gervasiolab.bsky.social @adrianmulholla1.bsky.social @rommieamaro.bsky.social Qiang Cui Matteo Dal Peraro #SBDD25

Huntington's disease successfully treated for first time One of the most devastating diseases finally has a treatment that can slow its progression and transform lives, tearful doctors tell BBC.

Absolutely remarkable from my colleagues @ucl.ac.uk

My dear friend Keshav Desiraju. passed away this day, four years ago. He was the force behind the Mental Health Act in India and the initiator of all the gutka bans that have/have not been implemented. You’re dearly missed my friend.

LUSH

Old Trafford stadium should be turned into an ice hockey rink.

Amazed to find @eduroam.org at GVA. Anyone knows why an international airport would have that? So far the only airport that I have passed through that has it. Any one knows other airports that have eduroam?

Publishing houses make millions, yet their platforms for reviewing are awful. Editorial Manager has to be the worst. What I don’t understand is why do you want me to register every time I get on your platforms @sciencedirect.bsky.social I refuse to engage anymore for reviewring.

Peer Review sections are now my favourite part of the manuscript. Here is a nugget from deep dark editorial world of @natcomms.nature.com

That is not true. Do you want me to put the email up here?

The reviewers’ evaluations highlight substantial issues with both the methodology and overall impact of the work. This was conveyed to us without any comments from the reviewers. This is the level of peer reviewing transparency @chemicalscience.rsc.org Arbitrary and vague.

Four professors, summer bbq and a garden. That what was the weekend about.

Mahmoud Farshchian’s work will live forever on. Rest in peace Ustad.

DNA-Programmable Protein Degradation: Dynamic Control of Proteolysis-Targeting Chimera Activity via DNA Hybridization and Strand Displacement Targeted protein degradation is a powerful therapeutic approach: expanding the druggable proteome, providing enhanced selectivity, and having the ability to overcome conventional resistance mechanisms...

We have developed a dynamic ‘off’ switch for PROTAC activity by using DNA linkers and toehold mediated strand displacement!

Published in JACS Au @pubs.acs.org

Led by Disha Kashyap, with @shozebhaider.bsky.social + Tom Milne

@uclchemistry.bsky.social #chemsky 🧪🧬
pubs.acs.org/doi/10.1021/...

Our latest work out in @angewandtechemie.bsky.social on what happens to PETase functions at the Solid‐Liquid Interface. With excellent work by my PhD student Shuang Chen @ucllifesciences.bsky.social

Paper: onlinelibrary.wiley.com/doi/10.1002/...

Why is @rsc.org flagship journal @chemicalscience.rsc.org so poor in its editorship. It’s not even a top flight journal and has taken 4 months to get us our first set of reviews. Never reviewing or submitting again to this journal.

Stellar line up for the @rsc.org Nucleic Acids Forum 2025 at The Burlington House. @drmikebooth.bsky.social opening the proceedings

Shozeb Haider explains his love for Guanine at the Biochemical Society AlterNAT meeting.

What's your favourite nucleobase?

@shozebhaider.bsky.social
@rsc.org
@biochemsoc.bsky.social

#chemsky

RNA: Searching for druggable targets A strategy that analyzes the structural properties of RNA could help identify regions that are promising targets for antiviral drugs.

An editorial on our work publsihed in @elife.bsky.social
@ucllifesciences.bsky.social #GQuadruplex

There is something extraordinary about New York and New Yorkers.

UK finally unveils £54 million global talent scheme Much-anticipated package for recruiting foreign researchers follows similar moves by France and the European Union to snap up US scientists

In case you're a researcher keen to flee to the UK.

'A £54 million “global talent fund” will cover relocation and research costs for “world-class” researchers and their teams to move to the UK....the fund will also cover full visa costs.' 1/2

Insights into the Enhanced Ceftazidime Hydrolysis by Ent385 AmpC β-Lactamase from Multiscale Simulations The emergence of multidrug-resistant bacteria poses a significant threat to public health. Particularly, they are becoming increasingly resistant to β-lactam antibiotics, which are one of the most important drug classes for the treatment of bacterial infections. Ceftazidime-avibactam has shown promising activity against highly drug-resistant bacteria, including carbapenem-resistant Enterobacterales. However, an Ala294-Pro295 deletion in the Class CE. cloacaeAmpC β-lactamase can confer reduced susceptibility to these agents. In this study, we investigated the molecular mechanisms underlying the enhanced hydrolysis of ceftazidime by E. cloacae Ent385 AmpC β-lactamase with the deletion using quantum mechanics/molecular mechanics (QM/MM) simulations. We used constant pH molecular dynamics simulations of the β-lactamase-ceftazidime acyl-enzyme complex to verify the likely protonation states, confirming Tyr150 primarily exists as a tyrosinate. We then used QM/MM (DFTB2/ff14SB) umbrella sampling to calculate the reaction-free energy barriers (Δ‡G) for the deacylation step of cephalosporin hydrolysis. This reveals that Tyr150 (rather than the substrate) acts as the base. Importantly, the difference in Δ‡G between the canonical E. cloacae AmpC (P99) and the Ent385 variant with Ala294-Pro295 reinserted, on the one hand, and the Ent385 variant, on the other, was in very good agreement with the difference deduced from experimental kinetic data. Detailed analysis of the transition state ensembles, alongside additional simulations, shows that the Ala294-Pro295 deletion allows the entrance of an additional water molecule that helps stabilize the tetrahedral intermediate. Overall, our QM/MM simulations provide valuable insights into the reaction mechanism and reasons for enhanced ceftazidime breakdown. The protocol used in this study successfully captures the kinetic differences observed among the studied variants. This approach can be employed to investigate other Class C β-lactamase variants with similar features, providing insights into their mechanisms and potential contributions to reduced susceptibility to antibiotic treatments.

Our first foray into Class C beta-lactamases - explaining how #antibiotic ceftazidime is broken down more easily by AmpC variants.
#AMR
#enzymes
#compchem

Great work by @andersonlimaaa.bsky.social, as @royalsociety.org fellow

ACS Catalysis (Open Access): pubs.acs.org/doi/10.1021/...

Conformational Landscape of the Di- and Tripeptide Permease A Transport Cycle Dipeptide and tripeptide permease A (DtpA) transporter is a bacterial homologue of the human PepT that is responsible for the uptake of di- and tripeptides from the small intestine and transports them...

In our latest work, we look at the different conformational states of DtpA in its transport cycle. @ucllifesciences.bsky.social

pubs.acs.org/doi/10.1021/...

Prof Shozeb Haider explaining the importance of dynamics when studying ligands targeting G-Quadruplex DNA structures.
@shozebhaider.bsky.social
@ucllifesciences.bsky.social

SAND: a comprehensive annotation of class D β-lactamases using structural alignment-based numbering | Antimicrobial Agents and Chemotherapy Class D β-lactamases (DBLs) form a large family with nearly 1,300 identified members in the β-Lactamase Database (Fig. S1, www.bldb.euhttp://www.bldb.eu/) (1). They are produced mainly by Gram-negative bacteria, with some by Gram-positive bacteria (2). DBLs are an important mechanism of resistance to β-lactam antibiotics, including carbapenems, one of last resort treatments to infections in hospitalized patients (3). The production of class D β-lactamases is a major public health concern, as they can often transfer between different bacterial species, allowing resistance to spread quickly and widely. Some members were found to be membrane-bound and are secreted via outer membrane vesicles (OMVs) to contribute further in antimicrobial resistance dissemination (4). Their mechanism of action involves a catalytic serine, as in classes A and C β-lactamases, since all share the conserved SXXK tetrad and KXG triad (3).

This unified framework streamlines cross-study comparisons and enhance data interpretation. Moreover, this standardized framework will enable AI-driven natural language processing (NLP) techniques to efficiently mine and compile relevant data from scientific literature. 3/3