Englander is known for his development of the field of hydrogen exchange (HX) studies. His group developed leading methods for HX measurement, accurately calibrated all aspects of protein and nucleic acid HX chemistry, and decisively settled the fundamental bases of HX interpretation in terms of H-bonded structure, detailed structural dynamics, and energetics. He used HX to explain a number of biomolecular problems including nucleic acid and protein “breathing” reactions and site-resolved energy transfer and utilization in hemoglobin allostery. He discovered protein “foldons” and demonstrated their fundamental role in stepwise sequential protein folding pathways. Recent work appears to explain the structure/energy cycle for ATP-driven unfolding by the superfamily of AAA+ proteins.

Research Interests

Most of our work concerns a naturally occurring process known as hydrogen exchange and its use to learn about the structure and behavior of biological macromolecules. My wife Joan and I and our colleagues have elaborated the chemistry of protein and nucleic acid hydrogen exchange processes and formulated the physical models for the internal protein and nucleic acid motions that determine the exchange rates of their individual hydrogens. We developed hydrogen exchange labeling methods and have used them to measure the energetic stability of individual bonding interactions and of the whole protein molecule to detect the parts of a protein responsible for regulatory structure change and function, and to describe the structure of transient kinetic folding intermediates that exist for less than one second. We developed a method that searches the manifold of high energy excited state intermediates available to any given protein molecule. These states depict the protein's cooperative submolecular design, define the intermediate forms that carry the protein from its unfolded to its native state in the folding process, and may recapitulate the steps in its biological evolution.

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Primary Section

Section 29: Biophysics and Computational Biology

Secondary Section

Section 21: Biochemistry