Adriaan Bax, Ph.D.

Our laboratory develops and applies nuclear magnetic resonance (NMR) methods to obtain more complete and quantitative descriptions of biomolecular structure and dynamics. We focus on processes that are difficult to capture by conventional structural methods, including protein folding and misfolding, transient conformational states, and dynamic interactions between macromolecules.

Current Research

Our work combines NMR methodology development with applications to proteins and other biological samples. Current efforts emphasize three areas:

Quantitative structure and dynamics. We improve measurements of interatomic distances, dihedral angles, chemical shifts, residual dipolar couplings, and molecular dynamics, and develop computational approaches that translate these data into more accurate descriptions of protein structure and motion. These measurements also provide stringent experimental tests of structural models derived from other experimental and computational approaches.

Time-resolved protein folding and misfolding. Rapid pressure changes inside an NMR sample cell shift protein folding equilibria and allow us to follow short-lived conformations as proteins fold, unfold, or oligomerize. Pressure-jump NMR provides residue-specific kinetic and structural information and has recently enabled structural characterization of a transient protein-folding intermediate.

New analytical applications. We are developing noninvasive methods to collect microscopic particles generated deep in the lung during breathing and to quantify their chemical composition using NMR and mass spectrometry. This approach is designed to provide chemically specific information about peripheral airway-lining fluid without invasive sampling.

We also develop pulse sequences, software, and web-based analysis tools and make these resources broadly available to the research community.

Applying our Research

NMR is particularly well suited to studying biomolecules in solution and to detecting states that are transient, weakly populated, or structurally heterogeneous. By increasing the accuracy, speed, and range of NMR measurements, our work aims to reveal mechanisms of protein folding, misfolding, oligomerization, and molecular recognition at atomic detail. These insights are relevant to diseases associated with aberrant protein assembly, while the underlying methods are broadly applicable across structural biology. Our respiratory work explores a complementary application: noninvasive access to the chemistry of peripheral airway-lining fluid for studies of lung physiology and disease.

Need for Further Study

Important challenges remain in obtaining reliable structural information from fleeting or heterogeneous biomolecular states and in combining experimental restraints with increasingly powerful computational structure models. Further gains in NMR sensitivity, time resolution, and quantitative interpretation should make it possible to characterize more complex systems and rarer states. For respiratory sampling, larger studies will be needed to establish biological variability and determine which chemical signatures are most informative for studies of lung physiology and disease.

• NIH Distinguished Investigator, Laboratory of Chemical Physics, NIDDK, NIH, 2005-present
• Chief, Biophysical Nuclear Magnetic Resonance Spectroscopy Section, Laboratory of Chemical Physics, NIDDK, NIH, 1991-present
• Visiting Scientist, Laboratory of Chemical Physics, NIDDK, NIH, 1983-1991
• Postdoctoral Associate, National Solid State NMR Facility, Colorado State University, 1982-1983
• Research Fellow, Delft University of Technology and Physical Chemistry Laboratory, University of Oxford, 1978-1981
• Ph.D., Applied Physics, Delft University of Technology, 1981
• B.S., Applied Physics, Delft University of Technology, 1978
• Selected honors: Robert A. Welch Award in Chemistry, 2018; National Academy of Sciences Award for Scientific Reviewing, 2018; Hinshelwood Lecturer, University of Oxford, 2012; American Institute of Chemists Gold Medal, 2026.