Abstract Cellular function is driven by the activity of proteins in stable complexes. Protein complex assembly depends on the direct physical association of component proteins. Advances in macromolecular structure prediction with tools like AlphaFold and RoseTTAFold have greatly improved our ability to model these interactions in silico, but an all-by-all analysis of the human proteome’s ~200 M possible pairs remains computationally intractable. A comprehensive cellular map of direct protein interactions will therefore be an invaluable resource to direct screening efforts. Here, we present DirectContacts2 , a machine learning model that distinguishes direct from indirect protein interactions using features derived from over 25,000 mass spectrometry experiments. Applied to ~25 million human protein pairs, our model outperforms previous resources in identifying direct physical interactions and enriches for accurate structural models including ~2500 AlphaFold3 models. Our framework enables structural modeling of disease-relevant complexes (e.g. orofacial digital syndrome (OFDS) complex) offering insights into the molecular consequences of pathogenic mutations (OFD1) and broadly, establishes a highly accurate protein wiring diagram of the cell.
A major puzzle in high-Tc superconductivity is the origin of the “Planckian” relaxation rate 1/τ underlying the linear-in-temperature resistivity in the strange-metal state, which persists up to very high temperatures. Implicit in theoretical discussions is the assumption that 1/…
Abstract We demonstrate that standard wafer fabrication can produce free-standing, mechanically stable, doubly-curved 3D structures with prescribed Gaussian curvature — a capability not previously achieved through semiconductor manufacturing. The stability of the deployed structu…
Recent work suggests that soil-borne viruses play an important role in controlling carbon (C) cycling and stocks. However, the contribution of individual prophage (i.e., temperate phages residing within bacterial hosts during lysogenic cycle) to C degradation remains largely undo…
Flexible impact-resistant materials are essential for defense, transportation, and biomedical engineering due to their ability to combine strength, energy dissipation, and compliance. While nature offers robust solutions like beetle elytra or mantis shrimp hammers, designing mate…
Abstract Hereditary transthyretin amyloidosis (ATTRv) is a fatal autosomal dominant disease characterized by systemic deposition of transthyretin (TTR) amyloid fibrils, leading to progressive neuropathy and cardiomyopathy. More than 130 pathogenic mutations in the TTR gene have b…
Abstract Soil moisture across South America exhibits coherent spatial patterns shaped by upwind terrestrial conditions, yet their downwind propagation remains poorly quantified. We develop an observation-driven framework integrating atmospheric transport trajectories with deep le…