The vast majority of missense variants observed in the human genome are of unknown
clinical significance. We present AlphaMissense, an adaptation of AlphaFold fine-tuned on …

Predicting the effects of mutations in proteins is critical to many applications, from
understanding genetic disease to designing novel proteins to address our most pressing …

Unveiling how genetic variations lead to phenotypic variations is one of the key questions in
evolutionary biology, genetics, and biomedical research. Deep mutational scanning (DMS) …

RAS proteins are conserved guanosine triphosphate (GTP) hydrolases (GTPases) that act
as molecular binary switches and play vital roles in numerous cellular processes. Upon GTP …

Protein functions are dynamically regulated by allostery, which enables conformational
communication even between faraway residues, and expresses itself in many forms, akin to …

We present MoCHI, a tool to fit interpretable models using deep mutational scanning data.
MoCHI infers free energy changes, as well as interaction terms (energetic couplings) for …

There are more ways to synthesize a 100-amino acid (aa) protein (20100) than there are
atoms in the universe. Only a very small fraction of such a vast sequence space can ever be …

Energetic local frustration offers a biophysical perspective to interpret the effects of
sequence variability on protein families. Here we present a methodology to analyze local …

Targeted protein degradation (TPD) is an emerging pharmacologic strategy. It relies on
small-molecule “degraders” that induce proximity of a component of an E3 ubiquitin ligase …

The encoding and evolution of specificity and affinity in protein-protein interactions is poorly
understood. Here, we address this question by quantifying how all mutations in one protein …