Protein kinases are central to biological regulation, dysregulated in many diseases, and the targets of a hundred clinically-approved drugs. Structural conservation of kinase active sites makes the de...

Mutations at sites distant from a protein’s active site can disrupt function through allosteric mechanisms. Here, authors present evidence that allostery is a widespread and underappreciated cause of ...

The bacteriophage ΦX174 was the first genome to be sequenced and the first to be chemically synthesised. Here we present a complete map of the consequences of changing every nucleotide in the ΦX174 ge...

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Comprehensive allosteric mapping prioritizes all possible druggable surface pockets in the Src kinase for allosteric inhibition.

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Transcription factors (TFs) bind specific DNA sequences to control gene expression. Modulating TF activity is of considerable therapeutic interest but very few TFs have been successfully drugged. TF D...

The use of neural networks to model genomic data in sequence-to-function scenarios has soared over the last decade. There remains much debate about whether these models are interpretable, either inher...

Many functions of proteins are performed by independently folding structural units called domains. The structures of domains are conserved during evolution but they are not identical. For example, the...

Allosteric communication between non-contacting sites in proteins plays a fundamental role in biological regulation and drug action. While allosteric gain-of-function variants are known drivers of onc...

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The aggregation rates of >140,000 mutants reveal the energetic structure of an amyloid-β nucleation reaction transition state.

Many proteins function as switches, detecting chemicals and transducing their concentrations into cellular responses. Receptor switches are key to the integration of environmental signals, yet it is n...

Many proteins function as switches, detecting chemicals and transducing their concentrations into cellular responses. Receptor switches are key to the integration of environmental signals, yet it is n...

G-protein coupled receptors (GPCRs) are the most abundant class of human receptors and drug targets. The vast majority of GPCR drugs bind the conserved orthosteric pocket, which can lead to non-specif...

At the Clinical Atlas of Variant Effects meeting (CLAVE meeting, July 2024, Pittsburgh USA), we developed recommendations for a draft atlas that can be realized by 2030, with a focus on empowering gen...

xAI trained on >100,000 random peptides predicts and elucidates primary sequence determinants of aggregation.

Nature Biotechnology - Metabolites can be quantified using a combination of aptamers and DNA barcodes.

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We lack tools to edit DNA sequences at scales necessary to study 99% of the human genome that is noncoding. To address this gap, we applied CRISPR prime editing to insert recombination handles into re...

Reduced protein stability is the most frequent mechanism by which rare missense variants cause disease. A promising therapeutic avenue for treating destabilizing variants is pharmacological chaperones...

An ingenious large-scale experiment in Barcelona has led to the creation of a catalog detailing the effects of half a million DNA mutations

From transforming coal to computing with DNA to pharmaceutical manufacturing in space, these are the discoveries that will set the stage for the next decade’s technology.

Reduced protein stability is the most frequent mechanism by which rare missense variants cause disease. A promising therapeutic avenue for treating destabilizing variants is pharmacological chaperones...

The world’s first joint research program in evolutionary medical genomics has been launched in Barcelona, under the direction of biologist Manuel Irimia