Exciting Instruments

Your molecules are doing something exciting, let's find out what!

We’re visiting labs and conferences across Europe and Boston over the next few weeks. Come meet us 👇

“Ultimately, in the core facility, we see a real broad range of use cases for the EI-FLEX, from basic physics all the way up to biomedicine.”

We had the pleasure of sitting down with Alex Payne-Dwyer, Senior Technical Specialist in the Bioscience Technology Facility at the University of York, who shared his experiences of running an EI-FLEX in a core facility.

We are also grateful to Facility Director Peter O'Toole for his input in the discussion.

🙌 From training new students in a matter of hours to discussing the EI-FLEX publications that have already emerged from the facility, Alex describes the possibilities that democratised biophysics now brings to the institute and how you can make the most of having an EI-FLEX in your own facility.

Read the interview here: excitinginstruments.com/resource-libra…

#corefacility #biophysics #singlemolecule #smfret #researchtechnology

Curious to see how Doxsey and Shen used the EI-FLEX to resolve ligand-induced conformational changes in Rag GTPase?

Specifically, they collected smFRET measurements across a range of conditions to discern how the global structure of Rag GTPase changes and drives downstream signalling in response to cellular amino acid sensing.

Overview of this application note:

🔄 Rag GTPase binding of guanine diphosphate (GDP) and/or guanine triphosphate (GTP) drives global conformational changes that differ depending on the combination of bound nucleotides

🤝 Dual binding of GTP induces inter-subunit cross-talk that stabilises Rag GTPase in order for hydrolysis to occur

🧬 Mutations in the nucleotide-binding domain that hyperactivate or inhibit mTORC signalling can be linked to Rag GTPase structural changes, independent of correct nucleotide binding

🔓 Binding of the mTORC subunit Raptor causes Rag GTPase to adopt an open, bound conformation

Ready to see how you could apply these techniques to your own protein-ligand systems? Read the full application now:

excitinginstruments.com/resource-libra…

#smfret #raggtpase #proteinconformation #proteindynamics

You know your molecules are binding - but do you understand how they interact?

In targeted protein degradation, binding affinity is only part of the story. Researchers also need to know whether proteins come together in the right orientation, whether cooperativity exists, and whether those interactions are likely to drive degradation.

As therapeutic mechanisms become more sophisticated, our analytical approaches need to evolve alongside them.

That's exactly what we'll explore in this week's Exciting Seminar with Dr Stefan Mueller, where he'll demonstrate how fluorescence cross-correlation spectroscopy (FCCS) enables direct characterisation of ternary complexes and higher-order protein interactions.

📅 20th August

Register here: us06web.zoom.us/meeting/regist…

#drugdiscovery #TPD #targetedproteindegradation #PROTAC #molecularglues #FCCS #singlemolecule

🧬 The biological world exists across energy landscapes, involving transient intermediates, rate-limiting conformational shifts, and complex binding equilibria.

In order to derive understanding from this energetic chaos, we have perfected observing biology in snapshots, from frozen or crystalline structures to averaged readouts of our cells fixed in a moment in time.

This has provided a wealth of information, but omits a key component of life, from the subcellular to the macroscopic: biology is dynamic.

To truly understand these systems, we need to view them as they are, in solution and in motion, observing individual molecules to find the rare intermediates that would otherwise be lost amongst the average.

In this article, we explore three techniques (smFRET, FCS, and FCCS) that capture these vital in-solution dynamics, highlighting case studies where these methods revealed mechanistic insights, linking structure to function:

🔄 How smFRET captures the global conformational changes induced by nucleotide binding of Rag GTPase and the allosteric impact of mutations in the nucleotide binding domain
🦠 The use of smFRET and FCS to investigate the mechanism of action of two distinct antiviral drugs against SARS-CoV-2 RNA-dependent RNA polymerase
🔗 How FCCS characterises ternary complex formation and kinetics, from cooperativity to stability

Curious to see the data? Access the full article here > excitinginstruments.com/resource-libra…
#smfret #fcs #fccs #biophysics #mechanisticinsights #article