Daniel Herschlag

About

We study biology through the lens of chemistry and physics, as the physical and chemical properties of biomolecules enable and constrain what biology can do and how it has evolved. Chemistry and physics are needed to understand and predict biology and to manipulate and engineer biological systems for biomedical and other applications. We focus on questions of how enzymes work, how RNA folds, how proteins recognize RNA, RNA/protein interactions in regulation and control, and the evolution of molecules and molecular interactions.

Research topics

• Computer Science
• Biology
• Physics
• Biochemistry
• Chemistry
• Materials science
• Genetics
• Machine Learning
• Nanotechnology
• Data Mining

Selected publications

• How to measure and evaluate binding affinities

  eLife · 2020 · 530 citations

  Senior authorCorresponding

  Quantitative measurements of biomolecule associations are central to biological understanding and are needed to build and test predictive and mechanistic models. Given the advances in high-throughput technologies and the projected increase in the availability of binding data, we found it especially timely to evaluate the current standards for performing and reporting binding measurements. A review of 100 studies revealed that in most cases essential controls for establishing the appropriate incu…

  DOI

• Revealing enzyme functional architecture via high-throughput microfluidic enzyme kinetics

  Science · 2021 · 229 citations

  Systematic and extensive investigation of enzymes is needed to understand their extraordinary efficiency and meet current challenges in medicine and engineering. We present HT-MEK (High-Throughput Microfluidic Enzyme Kinetics), a microfluidic platform for high-throughput expression, purification, and characterization of more than 1500 enzyme variants per experiment. For 1036 mutants of the alkaline phosphatase PafA (phosphate-irrepressible alkaline phosphatase of Flavobacterium), we performed mo…

  DOI

• Parallel molecular mechanisms for enzyme temperature adaptation

  Science · 2021 · 130 citations

  Senior authorCorresponding

  The mechanisms that underly the adaptation of enzyme activities and stabilities to temperature are fundamental to our understanding of molecular evolution and how enzymes work. Here, we investigate the molecular and evolutionary mechanisms of enzyme temperature adaption, combining deep mechanistic studies with comprehensive sequence analyses of thousands of enzymes. We show that temperature adaptation in ketosteroid isomerase (KSI) arises primarily from one residue change with limited, local epi…

  DOI

• Rapid and accurate determination of atomistic RNA dynamic ensemble models using NMR and structure prediction

  Nature Communications · 2020 · 82 citations

  Biomolecules form dynamic ensembles of many inter-converting conformations which are key for understanding how they fold and function. However, determining ensembles is challenging because the information required to specify atomic structures for thousands of conformations far exceeds that of experimental measurements. We addressed this data gap and dramatically simplified and accelerated RNA ensemble determination by using structure prediction tools that leverage the growing database of RNA str…

  PublisherOA PDFDOI

• RNA conformational propensities determine cellular activity

  Nature · 2023-05-17 · 58 citations

  articleOpen access
  PublisherOA PDFDOI

Recent grants

• Quantitative, High-throughput Mechanistic Enzymology

  NIH · $5.9M · 2002–2027

• NIH Grant R37GM049243

  NIH · $4.2M · 2013

• Fundamental Studies of RNA Conformational Thermodynamics

  NIH · $2.7M · 2019–2024

Frequent coauthors

• Thomas R. Cech

  University of Colorado Boulder

  41 shared

• Sebastian Doniach

  Stanford University

  41 shared

• Joseph A. Piccirilli

  University of Chicago

  40 shared

• Patrick O. Brown

  Stanford University

  37 shared

• Suzanne J. Admiraal

  Michigan Medicine

  36 shared

• Rick Russell

  The University of Texas at Austin

  35 shared

• Joël Janin

  Centre National de la Recherche Scientifique

  32 shared

• Dominique Deville‐Bonne

  Sorbonne Université

  32 shared

Labs

• Herschlag LabPI

Education

• B.S., Chemistry

  University of California, Berkeley

  1984

• Ph.D., Chemistry

  Stanford University

  1989

Awards & honors

• Inducted into the American Academy of Arts and Sciences (202…

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