Edward P. O’Brien

Protein entanglement misfolding determines divergent fates: proteasomal degradation or persistence in near-native misfolded states

The paper investigates how protein entanglement misfolding affects proteasomal degradation in human cells, finding that entangled proteins are more likely to be ubiquitinated and degraded.

Natively entangled proteins are linked to human disease and pathogenic mutations likely due to a greater misfolding propensity

The paper investigates whether proteins with native entanglements are more prone to misfolding and associated with disease, finding significant statistical associations.

Detecting misfolded non-covalent lasso entanglements in protein structures, simulation trajectories, and mass spectrometry data

The paper introduces EntDetect, a tool to detect non-covalent lasso entanglements in protein structures, simulations, and mass spectrometry data, and demonstrates its application in identifying misfolded states.

Native entanglement misfolding contributes to age-associated structural changes across the Saccharomyces cerevisiae proteome

The paper examines age-related structural changes in yeast proteins using mass spectrometry and simulations, finding that entanglement misfolding contributes to proteome aging.

Phosphoglycerate Kinase Can Adopt a Topologically Misfolded Form that is More Stable than its Native State

This study identifies a topologically misfolded form of E. coli phosphoglycerate kinase that is more stable than its native state and resists denaturation.

A widespread protein misfolding mechanism is differentially rescued by chaperones based on gene essentiality

The paper identifies a widespread protein misfolding mechanism involving non-covalent lasso entanglement (NCLE) and shows that chaperones rescue it more effectively for essential proteins.

High-throughput Experimental Validation of Synonymous Mutation Neutrality in the Human Genome

The paper validates that synonymous mutations in the human genome rarely affect fitness, occurring 165-fold less frequently than non-synonymous mutations.

MutSigCVsyn: Identification of Thirty Synonymous Cancer Drivers

The paper introduces MutSigCVsyn, an algorithm to identify synonymous cancer drivers by accounting for mutational heterogeneity, and identifies 30 novel synonymous drivers in cancer whole-genome sequences.

Pairs of amino acids at the P- and A-sites of the ribosome predictably and causally modulate translation-elongation rates

The paper identifies amino acid pairs at the ribosome's P- and A-sites that predictably and causally modulate translation-elongation rates in yeast.

A Chemical Kinetic Basis for Measuring Translation Initiation and Elongation Rates from Ribosome Profiling data

The paper develops chemical kinetic methods to measure translation initiation, elongation, and codon-specific rates from ribosome profiling data, finding significant variability in codon translation rates.

Identifying A- and P-site locations on ribosome-protected mRNA fragments using Integer Programming

This paper uses Integer Programming to accurately identify A-site locations on ribosome-protected mRNA fragments from Ribo-Seq data, improving signal-to-noise ratio by utilizing a wider range of fragment sizes.