Ad Bax

Last updated
Adriaan (Ad) Bax
Born
Netherlands
Education Delft University of Technology
Known forMethods development for NMR, such as RDCs (Residual dipolar coupling)
AwardsBijvoet Medal of the Bijvoet Center for Biomolecular Research (1993)

E. Bright Wilson Award (2000)
National Academy of Sciences (2002)
Welch Award in Chemistry (2018)

National Academy of Sciences Award for Scientific Reviewing (2018)

Contents

Scientific career
Fields Nuclear magnetic resonance, biophysics
Institutions NIDDK, National Institutes of Health
Thesis Two-Dimensional Nuclear Magnetic Resonance in Liquids (1981)
Doctoral advisor Ray Freeman and Toon Mehlkopf
Website spin.niddk.nih.gov/bax

Adriaan "Ad" Bax (born 1956) is a Dutch-American molecular biophysicist. He was born in the Netherlands and is the Chief of the Section on Biophysical NMR Spectroscopy at the National Institutes of Health. He is known for his work on the methodology of biomolecular NMR spectroscopy.

Biography

Bax was born in the Netherlands. He studied at Delft University of Technology where he got his engineer's degree (Ir. degree) in 1978, and Ph.D. degree in applied physics in 1981, after spending considerable time working with Ray Freeman at Oxford University. He worked as a postdoc with Gary Maciel at Colorado State University, before joining the NIH's Laboratory of Chemical Physics in 1983. In 1994 he became correspondent of the Royal Netherlands Academy of Arts and Sciences. [1] He is currently the Chief of the Section on Biophysical NMR Spectroscopy at NIH. In 2002 he was elected a member of the National Academy of Sciences in the section on Biophysics and computational biology and a Fellow of the American Academy of Arts and Sciences. [2] Bax was awarded the 2018 NAS Award for Scientific Reviewing and the 2018 Welch Award in Chemistry. [3]

Work in NMR spectroscopy

Bax works in the field of biomolecular NMR spectroscopy, and has been involved in the development of many of the standard methods in the field. He collaborated extensively with fellow NIH scientists Marius Clore, Angela Gronenborn and Dennis Torchia in the development of multidimensional protein NMR. [4] Bax is a pioneer in the development of triple resonance experiments and technology for resonance assignment of isotopically enriched proteins. [5] [6] He was also heavily involved in the development of using residual dipolar couplings [7] and chemical shifts [8] for determining RNA [9] and protein structures. [10] Much of his recent work focuses on the roles of proteins in membranes. [11] [12] [13] He was the world's most cited chemist over two decades (1981-1997). [14] [15]

Work during COVID-19 pandemic

Using laser light scattering, Bax examined how speech-generated droplets and aerosols may be a dominant SARS-CoV-2 transmission mode that may be mitigated by wearing face coverings or face masks. [16] [17]

Related Research Articles

<span class="mw-page-title-main">Solid-state nuclear magnetic resonance</span>

Solid-state NMR (ssNMR) spectroscopy is a technique for characterizing atomic level structure in solid materials e.g. powders, single crystals and amorphous samples and tissues using nuclear magnetic resonance (NMR) spectroscopy. The anisotropic part of many spin interactions are present in solid-state NMR, unlike in solution-state NMR where rapid tumbling motion averages out many of the spin interactions. As a result, solid-state NMR spectra are characterised by larger linewidths than in solution state NMR, which can be utilized to give quantitative information on the molecular structure, conformation and dynamics of the material. Solid-state NMR is often combined with magic angle spinning to remove anisotropic interactions and improve the resolution as well as the sensitivity of the technique.

Nuclear magnetic resonance spectroscopy of proteins is a field of structural biology in which NMR spectroscopy is used to obtain information about the structure and dynamics of proteins, and also nucleic acids, and their complexes. The field was pioneered by Richard R. Ernst and Kurt Wüthrich at the ETH, and by Ad Bax, Marius Clore, Angela Gronenborn at the NIH, and Gerhard Wagner at Harvard University, among others. Structure determination by NMR spectroscopy usually consists of several phases, each using a separate set of highly specialized techniques. The sample is prepared, measurements are made, interpretive approaches are applied, and a structure is calculated and validated.

<span class="mw-page-title-main">HNCA experiment</span>

HNCA is a 3D triple-resonance NMR experiment commonly used in the field of protein NMR. The name derives from the experiment's magnetization transfer pathway: The magnetization of the amide proton of an amino acid residue is transferred to the amide nitrogen, and then to the alpha carbons of both the starting residue and the previous residue in the protein's amino acid sequence. In contrast, the complementary HNCOCA experiment transfers magnetization only to the alpha carbon of the previous residue. The HNCA experiment is used, often in tandem with HNCOCA, to assign alpha carbon resonance signals to specific residues in the protein. This experiment requires a purified sample of protein prepared with 13C and 15N isotopic labelling, at a concentration greater than 0.1 mM, and is thus generally only applied to recombinant proteins.

The heteronuclear single quantum coherence or heteronuclear single quantum correlation experiment, normally abbreviated as HSQC, is used frequently in NMR spectroscopy of organic molecules and is of particular significance in the field of protein NMR. The experiment was first described by Geoffrey Bodenhausen and D. J. Ruben in 1980. The resulting spectrum is two-dimensional (2D) with one axis for proton (1H) and the other for a heteronucleus, which is usually 13C or 15N. The spectrum contains a peak for each unique proton attached to the heteronucleus being considered. The 2D HSQC can also be combined with other experiments in higher-dimensional NMR experiments, such as NOESY-HSQC or TOCSY-HSQC.

Xplor-NIH is a highly sophisticated and flexible biomolecular structure determination program which includes an interface to the legacy X-PLOR program. The main developers are Charles Schwieters and Marius Clore of the National Institutes of Health. Xplor-NIH is based on a C++ framework with an extensive Python interface enabling very powerful and easy scripting of complex structure determination and refinement protocols. Restraints derived from all current solution and many solid state nuclear magnetic resonance (NMR) and X-ray scattering experiments can be accommodated during structure calculations. Extensive facilities are also available for many types of ensemble calculations where the experimental data cannot be accounted for by a unique structure. Many of the structure calculation protocols involve the use of simulated annealing designed to overcome local minima on the path of the global minimum region of the target function. These calculations can be carried out using any combination of Cartesian, torsion angle and rigid body dynamics and minimization. Currently Xplor-NIH is the most versatile, comprehensive and widely used structure determination/refinement package in NMR structure determination.

<span class="mw-page-title-main">Residual dipolar coupling</span>

The residual dipolar coupling between two spins in a molecule occurs if the molecules in solution exhibit a partial alignment leading to an incomplete averaging of spatially anisotropic dipolar couplings.

Residual chemical shift anisotropy (RCSA) is the difference between the chemical shift anisotropy (CSA) of aligned and non-aligned molecules. It is normally three orders of magnitude smaller than the static CSA, with values on the order of parts-per-billion (ppb). RCSA is useful for structural determination and it is among the new developments in NMR spectroscopy.

<i>Journal of Biomolecular NMR</i> Academic journal

The Journal of Biomolecular NMR publishes research on technical developments and innovative applications of nuclear magnetic resonance spectroscopy for the study of structure and dynamic properties of biopolymers in solution, liquid crystals, solids and mixed environments. Some of the main topics include experimental and computational approaches for the determination of three-dimensional structures of proteins and nucleic acids, advancements in the automated analysis of NMR spectra, and new methods to probe and interpret molecular motions.

Nuclear magnetic resonance crystallography is a method which utilizes primarily NMR spectroscopy to determine the structure of solid materials on the atomic scale. Thus, solid-state NMR spectroscopy would be used primarily, possibly supplemented by quantum chemistry calculations, powder diffraction etc. If suitable crystals can be grown, any crystallographic method would generally be preferred to determine the crystal structure comprising in case of organic compounds the molecular structures and molecular packing. The main interest in NMR crystallography is in microcrystalline materials which are amenable to this method but not to X-ray, neutron and electron diffraction. This is largely because interactions of comparably short range are measured in NMR crystallography.

CS-ROSETTA is a framework for structure calculation of biological macromolecules on the basis of conformational information from NMR, which is built on top of the biomolecular modeling and design software called ROSETTA. The name CS-ROSETTA for this branch of ROSETTA stems from its origin in combining NMR chemical shift (CS) data with ROSETTA structure prediction protocols. The software package was later extended to include additional NMR conformational parameters, such as Residual Dipolar Couplings (RDC), NOE distance restraints, pseudocontact chemical shifts (PCS) and restraints derived from homologous proteins. This software can be used together with other molecular modeling protocols, such as docking to model protein oligomers. In addition, CS-ROSETTA can be combined with chemical shift resonance assignment algorithms to create a fully automated NMR structure determination pipeline. The CS-ROSETTA software is freely available for academic use and can be licensed for commercial use. A software manual and tutorials are provided on the supporting website https://csrosetta.chemistry.ucsc.edu/.

Triple resonance experiments are a set of multi-dimensional nuclear magnetic resonance spectroscopy (NMR) experiments that link three types of atomic nuclei, most typically consisting of 1H, 15N and 13C. These experiments are often used to assign specific resonance signals to specific atoms in an isotopically-enriched protein. The technique was first described in papers by Ad Bax, Mitsuhiko Ikura and Lewis Kay in 1990, and further experiments were then added to the suite of experiments. Many of these experiments have since become the standard set of experiments used for sequential assignment of NMR resonances in the determination of protein structure by NMR. They are now an integral part of solution NMR study of proteins, and they may also be used in solid-state NMR.

Nuclear magnetic resonance chemical shift re-referencing is a chemical analysis method for chemical shift referencing in biomolecular nuclear magnetic resonance (NMR). It has been estimated that up to 20% of 13C and up to 35% of 15N shift assignments are improperly referenced. Given that the structural and dynamic information contained within chemical shifts is often quite subtle, it is critical that protein chemical shifts be properly referenced so that these subtle differences can be detected. Fundamentally, the problem with chemical shift referencing comes from the fact that chemical shifts are relative frequency measurements rather than absolute frequency measurements. Because of the historic problems with chemical shift referencing, chemical shifts are perhaps the most precisely measurable but the least accurately measured parameters in all of NMR spectroscopy.

Protein chemical shift re-referencing is a post-assignment process of adjusting the assigned NMR chemical shifts to match IUPAC and BMRB recommended standards in protein chemical shift referencing. In NMR chemical shifts are normally referenced to an internal standard that is dissolved in the NMR sample. These internal standards include tetramethylsilane (TMS), 4,4-dimethyl-4-silapentane-1-sulfonic acid (DSS) and trimethylsilyl propionate (TSP). For protein NMR spectroscopy the recommended standard is DSS, which is insensitive to pH variations. Furthermore, the DSS 1H signal may be used to indirectly reference 13C and 15N shifts using a simple ratio calculation [1]. Unfortunately, many biomolecular NMR spectroscopy labs use non-standard methods for determining the 1H, 13C or 15N “zero-point” chemical shift position. This lack of standardization makes it difficult to compare chemical shifts for the same protein between different laboratories. It also makes it difficult to use chemical shifts to properly identify or assign secondary structures or to improve their 3D structures via chemical shift refinement. Chemical shift re-referencing offers a means to correct these referencing errors and to standardize the reporting of protein chemical shifts across laboratories.

PREDITOR is a freely available web-server for the prediction of protein torsion angles from chemical shifts. For many years it has been known that protein chemical shifts are sensitive to protein secondary structure, which in turn, is sensitive to backbone torsion angles. torsion angles are internal coordinates that can be used to describe the conformation of a polypeptide chain. They can also be used as constraints to help determine or refine protein structures via NMR spectroscopy. In proteins there are four major torsion angles of interest: phi, psi, omega and chi-1. Traditionally protein NMR spectroscopists have used vicinal J-coupling information and the Karplus relation to determine approximate backbone torsion angle constraints for phi and chi-1 angles. However, several studies in the early 1990s pointed out the strong relationship between 1H and 13C chemical shifts and torsion angles, especially with backbone phi and psi angles. Later a number of other papers pointed out additional chemical shift relationships with chi-1 and even omega angles. PREDITOR was designed to exploit these experimental observations and to help NMR spectroscopists easily predict protein torsion angles from chemical shift assignments. Specifically, PREDITOR accepts protein sequence and/or chemical shift data as input and generates torsion angle predictions for phi, psi, omega and chi-1 angles. The algorithm that PREDITOR uses combines sequence alignment, chemical shift alignment and a number of related chemical shift analysis techniques to predict torsion angles. PREDITOR is unusually fast and exhibits a very high level of accuracy. In a series of tests 88% of PREDITOR’s phi/psi predictions were within 30 degrees of the correct values, 84% of chi-1 predictions were correct and 99.97% of PREDITOR’s predicted omega angles were correct. PREDITOR also estimates the torsion angle errors so that its torsion angle constraints can be used with standard protein structure refinement software, such as CYANA, CNS, XPLOR and AMBER. PREDITOR also supports automated protein chemical shift re-referencing and the prediction of proline cis/trans states. PREDITOR is not the only torsion angle prediction software available. Several other computer programs including TALOS, TALOS+ and DANGLE have also been developed to predict backbone torsion angles from protein chemical shifts. These stand-alone programs exhibit similar prediction performance to PREDITOR but are substantially slower.

Nitrogen-15 nuclear magnetic resonance spectroscopy is a version of nuclear magnetic resonance spectroscopy that examines samples containing the 15N nucleus. 15N NMR differs in several ways from the more common 13C and 1H NMR. To circumvent the difficulties associated with measurement of the quadrupolar, spin-1 14N nuclide, 15N NMR is employed in samples for detection since it has a ground-state spin of ½. Since14N is 99.64% abundant, incorporation of 15N into samples often requires novel synthetic techniques.

<span class="mw-page-title-main">G. Marius Clore</span> Molecular biophysicist, structural biologist

G. Marius Clore MAE, FRSC, FRS is a British-born, Anglo-American molecular biophysicist and structural biologist. He was born in London, U.K. and is a dual U.S./U.K. Citizen. He is a Member of the National Academy of Sciences, a Fellow of the Royal Society, a NIH Distinguished Investigator, and the Chief of the Molecular and Structural Biophysics Section in the Laboratory of Chemical Physics of the National Institute of Diabetes and Digestive and Kidney Diseases at the U.S. National Institutes of Health. He is known for his foundational work in three-dimensional protein and nucleic acid structure determination by biomolecular NMR spectroscopy, for advancing experimental approaches to the study of large macromolecules and their complexes by NMR, and for developing NMR-based methods to study rare conformational states in protein-nucleic acid and protein-protein recognition. Clore's discovery of previously undetectable, functionally significant, rare transient states of macromolecules has yielded fundamental new insights into the mechanisms of important biological processes, and in particular the significance of weak interactions and the mechanisms whereby the opposing constraints of speed and specificity are optimized. Further, Clore's work opens up a new era of pharmacology and drug design as it is now possible to target structures and conformations that have been heretofore unseen.

Dennis Torchia is an American biophysicist who specialized in NMR spectroscopy. He spent most of his career at the National Institute of Dental and Craniofacial Research (NIDCR), part of the United States National Institutes of Health, where he served as Chief of the Structural Biology Unit before his retirement in 2006.

<span class="mw-page-title-main">James J. Chou</span> American chemist

James J. Chou (周界文) is a Chinese American scientist and Professor of Biological Chemistry and Molecular Pharmacology at the Harvard Medical School. He is known for pioneering the use of Nuclear Magnetic Resonance (NMR) Spectroscopy to reveal the structural details of the membrane regions of cell surface proteins, particularly those of immune receptors and viral membrane proteins.

<span class="mw-page-title-main">Mei Hong (chemist)</span> Chinese-American chemist

Mei Hong is a Chinese-American biophysical chemist and professor of chemistry at the Massachusetts Institute of Technology. She is known for her creative development and application of solid-state nuclear magnetic resonance (ssNMR) spectroscopy to elucidate the structures and mechanisms of membrane proteins, plant cell walls, and amyloid proteins. She has received a number of recognitions for her work, including the American Chemical Society Nakanishi Prize in 2021, Günther Laukien Prize in 2014, the Protein Society Young Investigator award in 2012, and the American Chemical Society’s Pure Chemistry award in 2003.

<span class="mw-page-title-main">Alfred G. Redfield</span> American molecular biologist, physicist

Alfred G. Redfield was an American physicist and biochemist. In 1955 he published the Redfield relaxation theory, effectively moving the practice of NMR or Nuclear magnetic resonance from the realm of classical physics to the realm of semiclassical physics. He continued to find novel magnetic resonance applications to solve real-world problems throughout his life.

References

  1. ↑ "A. Bax". Royal Netherlands Academy of Arts and Sciences. Archived from the original on 21 July 2015. Retrieved 18 July 2015.
  2. ↑ "Book of Members, 1780-2010: Chapter B" (PDF). American Academy of Arts and Sciences . Retrieved May 28, 2011.
  3. ↑ "Welch Award in Chemistry". www.welch1.org.
  4. ↑ Clore, Marius G (2011). "Adventures in Biomolecular NMR" (PDF). In Harris, Robin K; Wasylishen, Roderick L (eds.). Encyclopedia of Magnetic Resonance. John Wiley & Sons. doi:10.1002/9780470034590. hdl:11693/53364. ISBN   9780470034590.
  5. ↑ Ikura M; Kay LE; Bax A (1990). "A novel approach for sequential assignment of 1H, 13C, and 15N spectra of proteins: heteronuclear triple-resonance three-dimensional NMR spectroscopy. Application to calmodulin". Biochemistry. 29 (19): 4659–67. doi:10.1021/bi00471a022. PMID   2372549.
  6. ↑ Lewis E Kay; Mitsuhiko Ikura; Rolf Tschudin, Ad Bax (1990). "Three-dimensional triple-resonance NMR spectroscopy of isotopically enriched proteins". Journal of Magnetic Resonance. 89 (3): 496–514. Bibcode:1990JMagR..89..496K. doi:10.1016/0022-2364(90)90333-5.
  7. ↑ Tjandra N; Grzesiek S; Bax A (1996). "Magnetic field dependence of nitrogen-proton J splittings in 15N-enriched human ubiquitin resulting from relaxation interference and residual dipolar coupling". Journal of the American Chemical Society. 118 (26): 6264–6272. doi:10.1021/ja960106n.
  8. ↑ Kontaxis G; Delaglio F; Bax A (2005). Molecular fragment replacement approach to protein structure determination by chemical shift and dipolar homology database mining. Methods in Enzymology. Vol. 394. pp. 42–78. doi:10.1016/s0076-6879(05)94003-2. ISBN   9780121827991. PMID   15808217.
  9. ↑ Boisbouvier A; Delaglio F; Bax A (2003). "Direct observation of dipolar couplings between distant protons in weakly aligned nucleic acids". Proceedings of the National Academy of Sciences of the United States of America. 100 (20): 11333–11338. Bibcode:2003PNAS..10011333B. doi: 10.1073/pnas.1534664100 . PMC   208757 . PMID   12972645.
  10. ↑ Bax A; Grishaev A (October 2005). "Weak alignment NMR: a hawk-eyed view of biomolecular structure". Curr. Opin. Struct. Biol. 15 (5): 563–70. doi:10.1016/j.sbi.2005.08.006. PMID   16140525.
  11. ↑ Maltsev AS; Chen J; Levine RL; Bax A (February 2013). "Site-specific interaction between α-synuclein and membranes probed by NMR-observed methionine oxidation rates". J. Am. Chem. Soc. 135 (8): 2943–6. doi:10.1021/ja312415q. PMC   3585462 . PMID   23398174.
  12. ↑ Lorieau JL; Louis JM; Bax A (March 2013). "The impact of influenza hemagglutinin fusion peptide length and viral subtype on its structure and dynamics". Biopolymers. 99 (3): 189–95. doi:10.1002/bip.22102. PMC   3532579 . PMID   23015412.
  13. ↑ Lakomek NA; Kaufman JD; Stahl SJ; Louis JM; Grishaev A; Wingfield PT; Bax A (April 2013). "Internal dynamics of the homotrimeric HIV-1 viral coat protein gp41 on multiple time scales". Angew. Chem. Int. Ed. Engl. 52 (14): 3911–5. doi:10.1002/anie.201207266. PMC   3610801 . PMID   23450638.
  14. ↑ "Citation Laureates: Chemistry". In Cites. Archived from the original on 2 November 2002.
  15. ↑ "50 Most Cited Chemists 1981-1997". pcb4122.univ-lemans.fr. Archived from the original on 1 March 2003. Retrieved 12 January 2022.
  16. ↑ Anfinrud, Philip; Stadnytskyi, Valentyn; Bax, Christina E.; Bax, Adriaan (2020-05-21). "Visualizing Speech-Generated Oral Fluid Droplets with Laser Light Scattering". New England Journal of Medicine. 382 (21): 2061–2063. doi: 10.1056/nejmc2007800 . ISSN   0028-4793. PMC   7179962 . PMID   32294341.
  17. ↑ Stadnytskyi, Valentyn; Bax, Christina E.; Bax, Adriaan; Anfinrud, Philip (2020-06-02). "The airborne lifetime of small speech droplets and their potential importance in SARS-CoV-2 transmission". Proceedings of the National Academy of Sciences. 117 (22): 11875–11877. Bibcode:2020PNAS..11711875S. doi: 10.1073/pnas.2006874117 . ISSN   0027-8424. PMC   7275719 . PMID   32404416.
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