E. Shakhnovich

A ribosome-associating chaperone mediates GTP-driven vectorial folding of nascent eEF1A

The paper identifies Ypl225w as a chaperone that facilitates GTP-driven co-translational folding of eEF1A by interacting with the ribosome and NAC.

Conserved interfaces mediate multiple protein-protein interactions in a prokaryotic metabolon

This study maps 1225 protein-protein interactions in E. coli's 1-carbon metabolism pathway, revealing conserved interfaces that mediate transient interactions and enhance metabolic flux.

Enzymatic metabolon improves kinetic efficiency of reaction-limited enzyme pathways

This study shows that metabolons enhance metabolic flux for reaction-limited enzymes but not diffusion-limited ones, suggesting an evolutionary strategy for compensating inefficiency through clustering.

Allosteric communication between ligand binding domains modulates substrate inhibition in adenylate kinase

This study investigates how AMP substrate inhibition in adenylate kinase is modulated by domain motions, showing that inhibitory concentrations of AMP increase domain closure and affect catalytic activity.

Cotranslational formation of disulfides guides folding of the SARS CoV-2 receptor binding domain

The paper investigates how disulfide bond formation during translation guides the folding of the SARS-CoV-2 RBD, showing that non-equilibrium mechanisms are required to prevent misfolding.

Phosphorylation sites are evolutionary checkpoints against liquid-solid transition in protein condensates

This study shows phosphorylation sites prevent liquid-solid transitions in FUS condensates by reducing β-sheet propensity and stabilizing liquid-like states.

The physics of liquid-to-solid transitions in multi-domain protein condensates

This study uses simulations to show how multi-domain RNA-binding proteins transition from disordered to ordered, solid-like structures, with implications for disease-related changes.

Effect of RNA on morphology and dynamics of membraneless organelles.

This study shows RNA promotes phase separation of protein clusters by acting as super-scaffolds, enabling liquid-like dynamics at low protein concentrations.

Metabolic response to point mutations reveals principles of modulation of in vivo enzyme activity and phenotype

The paper investigates how point mutations in DHFR affect E. coli metabolism and phenotype by analyzing dTTP levels and enzyme kinetics.

DBFOLD: An efficient algorithm for computing folding pathways of complex proteins

DBFOLD predicts protein folding pathways and transition rates by combining Monte-Carlo simulations with high-temperature unfolding simulations to account for non-native interactions.

Development of antibacterial compounds that block evolutionary pathways to resistance

This study identifies a compound that inhibits both wild-type and TMP-resistant variants of E. coli DHFR, delaying resistance development through efflux pump duplication.

Liquid-liquid microphase separation leads to formation of membraneless organelles

The paper shows that multi-valent proteins form micro-phase separated droplets through arrested macro-phase separation, which is dynamic and functional, unlike the static macro-phase separation predicted by traditional models.

Adaptation to mutational inactivation of an essential E. coli gene converges to an accessible suboptimal fitness peak.

The paper shows that adaptation to mutational inactivation of an essential E. coli gene converges to a suboptimal fitness peak through specific metabolic and proteomic changes.

Co-translational folding allows misfolding-prone proteins to circumvent deep kinetic traps

This paper shows co-translational folding helps misfolding-prone proteins avoid kinetic traps by optimizing nascent chain lengths and translation rates.

Conformational catalysis of cataract-associated aggregation in a human eye lens crystallin occurs via interface stealing.

This study reveals that wild-type HγD accelerates aggregation of the cataract-related W42Q variant through a mechanism called interface stealing, where intermolecular domain interactions outcompete native intramolecular stabilization.

Mutation rate variability as a driving force in adaptive evolution

The paper shows that mutation rate variability affects resistance fixation in bacterial populations under stress, with low and high stress leading to disproportionate hypermutation effects.

Growth tradeoffs produce complex microbial communities on a single limiting resource

The paper shows that variation in microbial growth traits on a single resource can produce higher-order ecological effects, leading to complex community dynamics.

ProteomeVis: a web app for exploration of protein properties from structure to sequence evolution across organisms’ proteomes

ProteomeVis explores protein evolution across S. cerevisiae and E. coli proteomes by analyzing structure, sequence, and organismal properties.

Tuning the course of evolution on the biophysical fitness landscape of an RNA virus

This study predicts the evolutionary pathway of norovirus escaping antibodies using a biophysical fitness model, validated by experimental evolution in bulk culture and microfluidics.

Exploring the mutational robustness of nucleic acidsby searching genotype neighbourhoods in sequencespace

The paper uses in silico SELEX to study mutational robustness of an L-Arm binding aptamer, finding two functional genotype neighborhoods with similar binding affinity to the wild-type.