D. Herschlag

Exploring the energetic and conformational properties of the sequence space connecting naturally occurring RNA tetraloop receptor motifs

This study uses high-throughput thermodynamic measurements to explore how sequence changes affect the binding properties of RNA tetraloop receptor motifs, revealing complex sequence-fitness landscapes.

Conformational Ensembles Reveal the Origins of Serine Protease Catalysis

Ensemble-function analyses provide a quantitative model for serine protease catalysis, reveal previously unknown conformational features that contribute to their catalysis, and identify a structural motif that underlie these features and has evolved in >100 different enzymes from 32 protein folds.

Refinement of Multiconformer Ensemble Models from Multi-temperature X-ray Diffraction Data

This study refines multiconformer ensemble models from multi-temperature X-ray diffraction data of Proteinase K, revealing temperature-driven conformational changes and their functional implications.

Dissecting the energetic architecture within an RNA tertiary structural motif via high-throughput thermodynamic measurements

This paper uses high-throughput thermodynamic measurements to analyze the energetic architecture of an RNA tertiary motif, revealing non-linear cooperativity and exceptions to established stability-abundance relationships.

RNA conformational propensities determine cellular activity

The paper alters and measures conformational propensities of HIV-1 TAR RNA to predict binding affinities and cellular activity.

High-throughput enzymology reveals mutations throughout a phosphatase that decouple catalysis and transition state analog affinity

This study uses HT-MEK to analyze 1,004 PafA mutants, showing that distal mutations affect catalysis more than TSA binding, suggesting conformational changes influence enzyme function.

Ensemble-function relationships to evaluate catalysis in the ketosteroid isomerase oxyanion hole

The paper evaluates catalytic effects in ketosteroid isomerase by analyzing ensemble conformations and their functional implications.

Systematic investigation of the link between enzyme catalysis and cold adaptation

The paper investigates the link between enzyme catalysis and cold adaptation by analyzing kinetic constants and optimal growth temperatures, finding that rate variation is not strongly linked to cold adaptation.

Damaged goods? Evaluating the impact of X-ray damage on conformational heterogeneity in room temperature and cryo-cooled protein crystals

This study evaluates how X-ray damage affects conformational heterogeneity in protein crystals at room temperature and cryo-cooled conditions, finding that damage effects can be minimized or eliminated.

Revealing enzyme functional architecture via high-throughput microfluidic enzyme kinetics

HT-MEK, a microfluidic platform, reveals enzyme architectures shaping function through high-throughput kinetic analysis of enzyme variants.

Assessment of enzyme active site positioning and tests of catalytic mechanisms through X-ray-derived conformational ensembles

This study uses X-ray crystallography to analyze enzyme active site positioning and motions, finding limited conformational changes and challenging existing catalytic mechanisms.

An RNA dynamic ensemble at atomic resolution

This study determines an atomic-resolution RNA ensemble for HIV-1 TAR using structure prediction and NMR refinement, revealing cooperative conformational changes.

A Robust Method for Collecting X-ray Diffraction Data from Protein Crystals across Physiological Temperatures

This paper introduces a method for collecting high-resolution X-ray diffraction data from protein crystals at physiological temperatures, achieving high-quality data in under 5 seconds.

Quantitative studies of an RNA duplex electrostatics by ion counting

This study quantifies ion interactions with RNA and DNA duplexes, finding RNA attracts more cations and interacts stronger with Mg2+ than DNA.

Quantitative high-throughput tests of ubiquitous RNA secondary structure prediction algorithms via RNA/protein binding

The paper quantitatively tests RNA secondary structure prediction algorithms using RNA-MaP, revealing significant deviations between predictions and experimental stabilities.

Ion counting demonstrates a high electrostatic potential of the nucleosome

The paper measures nucleosome electrostatics and finds it retains a strong negative field despite charge reduction from DNA wrapping.

A quantitative and predictive model for RNA binding by human Pumilio proteins

The paper develops a predictive model for RNA binding by human PUM1 and PUM2 using RNA-MaP data, showing residue flipping and positional coupling, and validates it against in vivo crosslinking data.