Structura Biotechnology

Reminder to register for an upcoming in-person #CryoSPARC workshop in Toronto, delivered by @sickkidsto.bsky.social and the #CryoSPARC team, in partnership with the Canadian #CryoEM Nexus!
Deadline fast approaching!

Very excited for this in-person #CryoSPARC workshop in partnership with @sickkidsto.bsky.social and the Canadian #CryoEM Nexus! Register today!

Guide: Updating to CryoSPARC v5 (BETA) | CryoSPARC Guide CryoSPARC v5 is backwards compatible with v4. The update process includes new validation steps that may take some time, up to one hour for larger instances.

13/ A huge thanks to all those who helped test and provided feedback during the private beta!
We look forward to your feedback ahead of the general release!

See the full changelog at: cryosparc.com/updates/v5.0.0

Join the conversation at: discuss.cryosparc.com

12/ Updating to v5 includes validation of database contents, taking up to one hour for large instances.
Detailed update instructions, downgrade options and compatibility notes here: guide.cryosparc.com/setup-config...

11/ And finally, v5 connects the #CryoSPARC app with all of the detailed documentation (guide.cryosparc.com) that our team produces, with embedded docs links throughout the interface!

10/ Resource usage (GPU, CPU, and RAM) is now clearly visible across the interface, making it easier to diagnose bottlenecks, optimize scheduling and make better use of shared compute resources.

9/ Additional workflow improvements for #cryo-EM: Tags can now be created inline and applied to multiple jobs at once, parameters can be copied + pasted across jobs, and job info tags (job card stats) can be exported.

8/ Uploading external 3D volumes and masks into CryoSPARC is smoother. When Auto-Import is enabled, CryoSPARC will automatically create and queue an Import 3D Volumes job when .mrc or .map files are uploaded.

7/ In the tree view, upstream jobs are now collapsed into grouped cards, making it easy to stay focused on the jobs relevant to your workspace, and see where jobs from other workspaces are connected.

6/ The Job Dashboard brings all key outputs, plots, and diagnostics into one place. Interpret results at a glance and see changes over iterations. With the multi-job Comparison View, immediately spot differences and make decisions about the effect of a parameter or input change.

5/ v5 updates to CryoSPARC Live in make real-time processing easier under real-world data collection and hardware constraints. Delay the start of a Live session until new data arrives, auto pause when no new data has been found, and run multiple preprocessing workers per GPU.

4/ Homogeneous Ab-Initio Refinement enables refinement to high resolution from scratch, while preserving gold standard independence. Inspired by @olibclarke.bsky.social group’s results showing that Ab-Initio Reconstruction can improve map quality for small challenging targets.

3/ 3D refinements now perform per-particle scale optimization by default. The optimized values measure particle quality, used during reconstruction to down-weight low quality particles. The values can also be useful for separating low-quality particles from a dataset.

2/ Masking during 3D refinement has been significantly reworked. Dynamic mask generation now adapts automatically as resolution changes, reducing the likelihood of overfitting or overestimated resolution, without users needing to modify parameters.

🚀 CryoSPARC v5.0 BETA is here!

We’re excited to deploy another major #CryoSPARC release to help enable and accelerate #cryoEM data analysis. v5 has a redesigned underlying software system and many new features - highlights in thread!

Full changelog: cryosparc.com/updates/v5.0.0

Cryo-Electron Microscopy Cold Spring Harbor Laboratory Meetings & Courses -- a private, non-profit institution with research programs in cancer, neuroscience, plant biology, genomics, bioinformatics.

Interested in learning or strengthening skills in #CryoEM single particle analysis? Apply for the CSHL cryo-EM course happening in March! This is a super intense 2 week course covering theory up through data deposition. Apps due Jan 9! Info here: meetings.cshl.edu/courses.aspx...

Design, Synthesis, and Biological Evaluation of Mono- and Diamino-Substituted Squaramide Derivatives as Potent Inhibitors of Mycobacterial Adenosine Triphosphate (ATP) Synthase Amides of squaric acid are new drug candidates with activity against mycobacteria. Like the approved drug bedaquiline, these compounds achieve efficacy by inhibiting mycobacterial ATP synthase. Howeve...

Exciting collab with Paul Palme, Peter Imming, & Adrian Richter!
Guided by @courbongautier.bsky.social's structure of myco ATP synthase bound to a squaramide, they have made SQAs that are less toxic, more potent, more stable than AstraZeneca's SQ31f
#MedChem #TB #NTM
pubs.acs.org/doi/full/10....

Cryo-EM structure of endogenous Pfs230:Pfs48/45 complex with six antibodies reveals mechanisms of malaria transmission-blocking activity The Pfs230:Pfs48/45 complex forms the basis for leading malaria transmission-blocking vaccine candidates, yet little is known about its molecular asse…

Featured #paper shows mechanism of #malaria infection blocking. Read "Cryo-EM structure of endogenous Pfs230:Pfs48/45 complex with 6 antibodies reveals mechanisms of malaria transmission-blocking" by @utoronto.ca using our CMCF beamline. https://bit.ly/47TWrVv 👈

Structura Bio | Structura Bio

🚀 Hiring: Cryo-EM Application Scientist, Marketing!

Develop and deliver high-impact scientific marketing content, illustrate the value of new #CryoSPARC features and #cryoEM advances, and help scientists understand how our tools can help solve their problems.

structura.bio/careers/appl...

CAHRA 2025: Community-Wide Assessment of Cryo-EM Heterogeneous Reconstruction Algorithms A community-wide data processing challenge for cryo-electron microscopy.

Announcing cryo-EM heterogeneity challenge #2, now dubbed the 2025 Community-Wide Assessment of Cryo-EM Heterogeneous Reconstruction Algorithms (CAHRA)! Join us for a webinar next Friday (Nov 14th) to learn more. Datasets already posted here: heterogeneity.notion.site/challenge #cryoem

Cryo-EM maps and atomic models of the biotin-containing 3-methylcrotonyl-CoA carboxylase (MCC) complex and long-chain acyl-CoA carboxylase (LCC) complex

New lab preprint!
@zestytoast.bsky.social tagged a scarce mycobacterial protein in M. smegmatis with TwinStep but got… something? @kjamali.bsky.social's ModelAngelo built models & @martinsteinegger.bsky.social's FoldSeek IDed them as the biotin-containing MCC & LCC complexes
🧵
tinyurl.com/ukny4ptz

On a gruelling hunt for rare associated molecules in your #cryoEM particle stack and not sure where to look?

Discover practical tips and tricks in our new case study using #CryoSPARC v4.7.1 where we find and refine a low-population interaction partner!

guide.cryosparc.com/processing-d...

CryoSPARC | Automated Repeat‑Target Structure Determination An end‑to‑end, automated workflow for single‑particle cryo‑EM that achieves state‑of‑the‑art consensus maps suitable for model building—demonstrated across 21 GPCR datasets, meeting or exceeding publi...

At cryosparc.com/automated-workflows we provide instructions and CryoSPARC Workflow JSON files so that users can get started with automation easily.
Reach out at discuss.cryosparc.com/c/automated-workflows.
Happy processing!

Automated processing unlocks several benefits. Time-to-structure can be greatly reduced and throughput can be easily scaled for repeat-target use cases. Solving multiple structures per day can now become a reality. 🚀

The workflow is powered by new methods, including micrograph junk detection, denoising, and reference based auto selection of 2D classes and 3D volumes. Read the preprint for more insights and details.

The automated workflow generalizes easily to new target classes.
We provide downloadable #CryoSPARC Workflow JSON files so that users can replicate, adapt and extend it for their own targets. All required jobs and tools are already available in v4.7.1+.

In 10 of 21 cases, the automated results enable improved model building of the ligand, binding pocket, side chain positioning and/or extracellular loops. Three striking examples are shown here and in the first video.

We test across 21 challenging active and inactive GPCR datasets.
Despite small particle size and the presence of contaminants, empty micelles, broken, denatured and aggregated particles, our automated workflow yields equal or better resolution and map quality in 17 of 21 cases.

The automation strategy we have developed can be set up once for any specific target class (e.g. active state GPCRs with Nb35) and reused to process multiple datasets fully hands-off. It makes use of minimal prior knowledge through a low-res (15Å) 3D reference map.

🚀 Introducing fully automated data processing for repeat-target #cryoEM.

Using new tools in #CryoSPARC, it is now possible to obtain resolutions & map quality equal to or better than manual processing, with zero user intervention.

Preprint: www.biorxiv.org/content/10.1...