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Article
Open AccessThe energetic and allosteric landscape for KRAS inhibition
Thousands of proteins have been validated genetically as therapeutic targets for human diseases1. However, very few have been successfully targeted, and many are considered ‘undruggable’. This is particularly tru...
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Article
Map** the energetic and allosteric landscapes of protein binding domains
Allosteric communication between distant sites in proteins is central to biological regulation but still poorly characterized, limiting understanding, engineering and drug development1–6. An important reason for ...
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Article
Open AccessDiMSum: an error model and pipeline for analyzing deep mutational scanning data and diagnosing common experimental pathologies
Deep mutational scanning (DMS) enables multiplexed measurement of the effects of thousands of variants of proteins, RNAs, and regulatory elements. Here, we present a customizable pipeline, DiMSum, that represe...
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Article
Open AccessThe mutational landscape of a prion-like domain
Insoluble protein aggregates are the hallmarks of many neurodegenerative diseases. For example, aggregates of TDP-43 occur in nearly all cases of amyotrophic lateral sclerosis (ALS). However, whether aggregate...
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Article
3D structures of individual mammalian genomes studied by single-cell Hi-C
The folding of genomic DNA from the beads-on-a-string-like structure of nucleosomes into higher-order assemblies is crucially linked to nuclear processes. Here we calculate 3D structures of entire mammalian ge...
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Article
Open AccessCo-binding by YY1 identifies the transcriptionally active, highly conserved set of CTCF-bound regions in primate genomes
The genomic binding of CTCF is highly conserved across mammals, but the mechanisms that underlie its stability are poorly understood. One transcription factor known to functionally interact with CTCF in the co...
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Article
Open AccessInvestigating the effect of paralogs on microarray gene-set analysis
In order to interpret the results obtained from a microarray experiment, researchers often shift focus from analysis of individual differentially expressed genes to analyses of sets of genes. These gene-set an...
