Shakhnovich Biophysics Lab

Protein language models are trained on highly imbalanced datasets, raising the question of how they represent underrepresented biological sequences. Using viral proteins as a case study across ESM model families, we identify a dominant nativeness axis in...

Cotranslational protein folding follows a distinct pathway shaped by the vectorial emergence of the peptide and spatial constraints of the ribosome exit tunnel. Variations in translation rhythm can cause misfolding linked to disease; however, predicting...

We introduce foundational principles for designing customizable fitness landscapes for proteins. We focus on crafting antibody ensembles to create evolutionary traps which restrict viral fitness enhancement. By deriving a fundamental relationship between...

The early detection of high-fitness viral variants is critical for pandemic response, yet limited experimental resources at the onset of variant emergence hinder effective identification. To address this, we introduce an active learning framework that...

The effect of salt on coacervation of synthetic or biological polyelectrolytes is well-studied. However, recent experiments showed that largely neutral IDPs like FUS also undergo LLPS at physiological salt concentrations, dissolve at higher salt...

Eukaryotic translation elongation factor 1A (eEF1A) is a highly abundant, multi-domain GTPase. Post-translational steps essential for eEF1A biogenesis are carried out by bespoke chaperones but co-translational mechanisms tailored to eEF1A folding remain...

The bacterial protein quality control (PQC) network comprises a set of genes that promote proteostasis (proteome homeostasis) through proper protein folding and function via chaperones, proteases, and protein translational machinery. It participates in...

Biological condensates often emerge as a multidroplet state and never coalesce into one large droplet within the experimental timespan. Previous work revealed that the sticker-spacer architecture of biopolymers may dynamically stabilize the multidroplet...

Biological condensates often emerge as a multi-droplet state and never coalesce into one large droplet within the experimental timespan. Previous work revealed that the sticker-spacer architecture of biopolymers may dynamically stabilize the multi-droplet...

For over a century, an explanation for how concentrated ions denature proteins has proven elusive. Here, we report a novel mechanism of protein denaturation driven by entropy changes in water networks. Experiments and simulations show that ion pairs like...

The existence of multiple biomolecular condensates inside living cells is a peculiar phenomenon not compatible with the predictions of equilibrium statistical mechanics. In this work, we address the problem of multiple condensates state (MCS) from a...

SARS-CoV-2 employs its spike protein's receptor binding domain (RBD) to enter host cells. The RBD is constantly subjected to immune responses, while requiring efficient binding to host cell receptors for successful infection. However, our understanding of...