Weicheng
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weichengli.bsky.social
Weicheng
@weichengli.bsky.social
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Postdoc in Jon Ostrem Lab at UCSF. Chemical biology, and targeted cancer therapies.
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Reposted by Weicheng
lindorfflarsen.bsky.social
Integrative modelling of biomolecular dynamics

Time-dependent and -resolved experiments combined with computation provide a view on molecular dynamics beyond that available from static, ensemble-averaged experiments

Review w @dariagusew.bsky.social & Carl G Henning Hansen
doi.org/10.48550/arX...
Figure 1 from the review. Caption: Comparison of a schematic example showing static, time-dependent, and time-resolved experiments illustrated by a protein folding process. (a) A static experiment measuring the observable O$_{\text{exp}}$ is shown, which can be modelled as a distribution of simulated values, O$_{\text{calc}}$, representing a conformational ensemble of folded and unfolded states. (b) Shows a time-dependent experiment, where the equilibrium dynamics of reversible folding gives rise to measured transition times $\tau_1$ and $\tau_2$. These can be modelled as equilibrium dynamics, illustrated by a free energy (FE) surface along a chosen degree of freedom (D.O.F.) (c) A time-resolved experiment probes a non-equilibrium process, where the system begins at $t_{0}$ in the folded state. During the observation time $t$ the protein unfolds until $t_{\text{max}}$. At each time point, a distinct ensemble average, O$_{\text{exp}}$, can be observed, reflecting the proteins changing structure. This evolution can be modelled as distributions of O$_{\text{calc}}$ at each time point. These are shown together with a FE surface.
October 2, 2025 at 7:54 AM
Reposted by Weicheng
dangrabarczyk.bsky.social
Glad to share the final version of our story about the UBR4 complex, an E4 ligase protein quality control hub @science.org. Now with more cryo-EM structures and a deeper dive into substrate recognition, especially escaped mitochondrial proteins @clausenlab.bsky.social www.science.org/doi/10.1126/...
August 28, 2025 at 6:54 PM
Reposted by Weicheng
natchembio.nature.com
A new paper reports direct ubiquitination of a small molecule BRD1732 in cells. BR31732 ubiquitination is E3 ligase-dependent and leads to inhibition of proteasomal degradation.

www.nature.com/articles/s41...
Highly specific intracellular ubiquitination of a small molecule - Nature Chemical Biology
Li et al. discovered that the cytotoxic synthetic small molecule BRD1732 is directly ubiquitinated in cells. Ubiquitination of BRD1732 is E3 ligase dependent and leads to inhibition of proteasomal deg...
www.nature.com
August 21, 2025 at 4:25 PM
Reposted by Weicheng
chimerax.ucsf.edu
Here's how to predict binding of tens or hundreds of small molecules to protein assemblies using Boltz 2 in ChimeraX.
Accuracy depends on how similar the ligands and binding pockets are to existing experimental structures.
www.rbvi.ucsf.edu/chimerax/dat...
August 20, 2025 at 9:01 PM
Reposted by Weicheng
morstein.bsky.social
Excited to share our new @pubs.acs.org paper! We engineered cells with ~10% photolipids in the ER membrane. This enabled optical control of membrane viscosity to study its impact on ER→Golgi protein transport. @dirktrauner.bsky.social @noemijimenezrojo.bsky.social

pubs.acs.org/doi/10.1021/...
Optical Control of Membrane Viscosity Modulates ER-to-Golgi Trafficking
The lipid composition of cellular membranes is highly dynamic and undergoes continuous remodeling, affecting the biophysical properties critical to biological function. Here, we introduce an optical a...
pubs.acs.org
August 14, 2025 at 10:43 AM
Reposted by Weicheng
chrisgparker.bsky.social
Excited to share a new preprint from the lab. We show that PTMs like phosphorylation & glycosylation dynamically reshape proteome-wide ligandability in cells, including proteins like KRAS. Great collaboration with the Huang Lab, @forlilab.bsky.social and BMS. www.biorxiv.org/content/10.1...
Post-Translational Modifications Remodel Proteome-Wide Ligandability
Post-translational modifications (PTMs) vastly expand the diversity of human proteome, dynamically reshaping protein activity, interactions, and localization in response to environmental, pharmacologi...
www.biorxiv.org
August 3, 2025 at 2:36 PM
Reposted by Weicheng
kjohnsson.bsky.social
Finally out in Nature Chem Bio:
SNAP-tag2 for faster and brighter protein labeling
www.nature.com/articles/s41...
Thank you Steffi and Veselin.
SNAP-tag2 for faster and brighter protein labeling - Nature Chemical Biology
SNAP-tag is a widespread tool for labeling protein for bioimaging. Now, Kühn et al. report SNAP-tag2 with increased labeling kinetics and brightness, which translates into a better performance in live...
www.nature.com
July 3, 2025 at 7:45 PM
Reposted by Weicheng
fosterlab.bsky.social
Our latest paper hit the airwaves: www.pnas.org/doi/10.1073/... We linked subunits from the ring-forming, cooperative ligand binding protein TRAP, then used NMR, calorimetry, native MS and cryoEM to examine the role of nearest-neighbor interactions on cooperativity and structure. Congrats Team!
PNAS
Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans...
www.pnas.org
December 30, 2024 at 8:16 PM