Jane S. Richardson

Last updated

Jane S. Richardson
Jane S Richardson BW photo 2002.jpg
Richardson in 2002
Born (1941-01-25) January 25, 1941 (age 83)
Alma mater Swarthmore College, Harvard University
Known for Ribbon diagram, structure validation
SpouseDavid C. Richardson
Awards MacArthur Fellowship (1985), Alexander Hollaender Award in Biophysics (2019)
Scientific career
Fields Structural biology, Biophysics
Institutions Duke University
Ribbon schematic of Triosephosphate isomerase, hand-drawn by Jane Richardson TriosePhosphateIsomerase Ribbon pastel photo mat.png
Ribbon schematic of Triosephosphate isomerase, hand-drawn by Jane Richardson
All-atom contact dots for two well-packed Ala residues All-atomContacts 1gciAlas.jpg
All-atom contact dots for two well-packed Ala residues

Jane Shelby Richardson (born January 25, 1941) [1] [2] is an American biophysicist best known for developing the Richardson diagram, or ribbon diagram, a method of representing the 3D structure of proteins. [3] Ribbon diagrams have become a standard representation of protein structures that has facilitated further investigation of protein structure and function globally. With interests in astronomy, math, physics, botany, and philosophy, Richardson took an unconventional route to establishing a science career. [4] [5] Richardson is a professor in biochemistry at Duke University. [1]

Contents

Biography

Richardson was born on January 25, 1941, and grew up in Teaneck, New Jersey. Her father was an electrical engineer and her mother was an English teacher. Her parents encouraged an interest in science and she was a member of local astronomy clubs as early as elementary school. [6] She attended Teaneck High School and in 1958 won third place in the Westinghouse Science Talent Search, the most prestigious science fair in the United States, with calculations of the satellite Sputnik's orbit from her own observations. [7] [4]

She continued her education intending to study mathematics, astronomy and physics at Swarthmore College. However, Richardson instead graduated Phi Beta Kappa with a bachelor's degree in philosophy and a minor in physics in 1962 before she pursued graduate work in philosophy at Harvard University. Meanwhile, she was able to enroll in plant taxonomy and evolution courses at Harvard that would later contribute to her big-picture approach to studying protein structure. Since Harvard's philosophy focused on modern philosophy instead of Richardson's interest, classical philosophy, Richardson left with her master's degree from Harvard in 1966. [1] [8] [9] Post-graduation, Richardson tried teaching high school, but soon realized that this career path was not for her. She subsequently rejoined the scientific world, working as a technician at Massachusetts Institute of Technology in the same laboratory as her husband, David Richardson, whom she met at Swarthmore College. [10] At MIT, David Richardson was pursuing his doctorate in Al Cotton's lab using X-ray crystallography to study the structure of staphylococcal nuclease. Jane Richardson learned the necessary technical skills and scientific background in biochemistry and biophysics through work at the lab as she worked alongside her husband, whom she still works with today. Richardson later began drawing her eponymous diagrams as a method of interpreting the structures of protein molecules. [10] Over the course of her career, Richardson has been recognized by many prestigious institutions of the scientific community. In July 1985 she was awarded a MacArthur Fellowship for her work in biochemistry. [11] She was elected to the National Academy of Sciences and the American Academy of Arts and Sciences in 1991 and to the Institute of Medicine in 2006. [5] As part of her role in the National Academy of Sciences, Richardson serves on panels that advise the White House and the Pentagon regarding nationally important scientific matters (e.g., [12] ). For the 2012-2013 year, Richardson was elected president of the Biophysical Society for the 2012-2013 year, [13] and she became a fellow of the American Crystallographic Association in 2012. [14] Richardson is currently a James B. Duke Professor of Biochemistry at Duke University. [4]

The Richardsons continue to jointly head a research group at Duke University. [10]

Richardson is a contributor to Wikipedia, where she is a prominent member of WikiProject Biophysics. [15]

Scientific work and contributions

Richardson's first forays into science were in the field of astronomy. By observing the position of Sputnik – at the time, the only artificial satellite – on two successive nights, she managed to calculate its predicted orbit. She submitted her results to the Westinghouse Science Talent Search, winning third place in 1958. [5]

Richardson joined her husband David C. Richardson, then completing his PhD work at MIT, in studying the 3-dimensional structure of the staphylococcal nuclease protein (1SNS) [16] by X-ray crystallography for his doctoral thesis. [17] [18] Staphylococcal nuclease was among the first dozen protein structures solved. [19] Classes in botany and evolution that she had taken while pursuing her degree shaped her thinking about the work she was doing in the chemistry laboratory. [4] During her crystallographic studies, Jane Richardson had come to realize that a general classification scheme can be developed from the recurring structural motifs of the proteins. [4] In the meantime, Jane and David Richardson had moved to Duke University in 1970, where they solved the first crystal structure of superoxide dismutase (2SOD). [10] [20] [21] By 1977 she published her findings on protein relatedness in Nature , with a paper entitled "β-sheet topology and the relatedness of proteins". [4] [22]

As Richardson developed the ribbon diagram to illustrate her findings over the course of her taxonomic research, her iconic images first appeared in the review journal Advances in Protein Chemistry in an article titled "The anatomy and taxonomy of protein structure" 1981, [5] [23] [24] an early hallmark publication in structural bioinformatics. The diagrams have since become a standard way of visualizing protein structure, specifically depicting beta-sheet topology and connections between amino acid sequences, or peptides, that make up proteins. The protein folding process involves four levels: primary structures, secondary structures, tertiary structures, and quaternary structures. Secondary structures result from hydrogen bond interactions between adjacent amino acids sequences to form alpha helices or beta-sheets. [25] Tertiary structures are a higher order of protein folding that depict the conformation of and connectivity between alpha-helices and beta-sheets in 3D. [25] Richardson's ribbon diagrams illustrate beta-sheet topology and connectivity in higher-order protein structures. She formalized general rules about beta-sheets linkage via "hairpin" connections or "crossover" connections. In a hairpin connection a peptide backbone stems out of and loops around to return to the same beta-sheet end from which it left. A crossover connection involves the peptide backbone extending out of one beta-sheet and looping around to enter another beta-sheet on the opposite end of the protein. [26] Her initial drawings and continual discoveries contribute to a broader understanding of protein energetics and evolution. Peter Agre, Nobel laureate and fellow Duke professor, said of the Richardsons' work: "Jane and David’s work allowed us to reveal the form of proteins, and from there it was easier to understand their function". [10]

The Richardsons' more recent work has diversified beyond classification and crystallography. In the 1980s they stretched into the fields of synthetic biochemistry and computational biology as pioneers in the de novo design of proteins, a reverse engineering approach to make and test theoretical predictions about protein folding. [27] In the 1990s the Richardsons developed the kinemage system of molecular graphics and David Richardson wrote the Mage program to display them on small computers, for the then-new journal Protein Science. [28] Additionally, they developed all-atom contact analysis (see image) to measure "goodness of fit" inside proteins and in interactions with surrounding molecules. [4] The Kinemage website offers interactive exploration of various 3D protein structures through computer displays using their Mage or KiNG graphics programs. Funded by a National Institutes of Health (NIH) grant, the website is often used as a teaching tool. Textbooks and internet sites that have sourced images from Kinemages include Introduction to Protein Structure by Branden & Tooze, [29] Fundamentals of Biochemistry by Viet, Voet & Pratt, [30] Principles of Biochemistry by Horton et al., [31] and the University of Mississippi's Kinemage Authorship Project. [32]

The Richardson Laboratory currently studies structural motifs in RNA [33] as well as proteins, as part of the RNA Ontology Consortium (ROC) [34] to better communicate RNA structure and function research findings. [35] [36] The laboratory has acted as assessors in the CASP8 structure-prediction experiment [37] (CASP), [38] is one of the four developer teams on the PHENIX software system [39] for x-ray crystallography of macromolecules, and hosts the MolProbity web service [40] for validation and accuracy improvement of protein and RNA crystal structures. MolProbity uses the KiNG program (successor to Mage) for showing 3D kinemage graphics on-line. Jane Richardson serves on the worldwide Protein Data Bank (wwPDB) X-ray Validation Task Force [41] and NMR Validation Task Force. [42] As she continues to run the Richardson laboratory alongside her husband at Duke, where they use MolProbity to validate RNA, protein, crystal structures, she also adds science-related images, images of nature, and pictures for the WikiProject Biophysics to Wikimedia Commons. [15]

Awards and honors

Notable publications

The following articles are classified as highly cited in field by Web of Science as of February 17, 2020:

Related Research Articles

<span class="mw-page-title-main">Alpha helix</span> Type of secondary structure of proteins

An alpha helix is a sequence of amino acids in a protein that are twisted into a coil.

<span class="mw-page-title-main">Beta sheet</span> Protein structural motif

The beta sheet is a common motif of the regular protein secondary structure. Beta sheets consist of beta strands (β-strands) connected laterally by at least two or three backbone hydrogen bonds, forming a generally twisted, pleated sheet. A β-strand is a stretch of polypeptide chain typically 3 to 10 amino acids long with backbone in an extended conformation. The supramolecular association of β-sheets has been implicated in the formation of the fibrils and protein aggregates observed in amyloidosis, Alzheimer's disease and other proteinopathies.

<span class="mw-page-title-main">Biomolecule</span> Molecule that is produced by a living organism

A biomolecule or biological molecule is a loosely used term for molecules present in organisms that are essential to one or more typically biological processes, such as cell division, morphogenesis, or development. Biomolecules include large macromolecules such as proteins, carbohydrates, lipids, and nucleic acids, as well as small molecules such as vitamins and hormones. A more general name for this class of material is biological materials. Biomolecules are an important element of living organisms, those biomolecules are often endogenous, produced within the organism but organisms usually need exogenous biomolecules, for example certain nutrients, to survive.

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

A kinemage is an interactive graphic scientific illustration. It often is used to visualize molecules, especially proteins although it can also represent other types of 3-dimensional data. The kinemage system is designed to optimize ease of use, interactive performance, and the perception and communication of detailed 3D information. The kinemage information is stored in a text file, human- and machine-readable, that describes the hierarchy of display objects and their properties, and includes optional explanatory text. The kinemage format is a defined chemical MIME type of 'chemical/x-kinemage' with the file extension '.kin'.

<span class="mw-page-title-main">Ramachandran plot</span> Visual representation of allowable protein conformations

In biochemistry, a Ramachandran plot, originally developed in 1963 by G. N. Ramachandran, C. Ramakrishnan, and V. Sasisekharan, is a way to visualize energetically allowed regions for backbone dihedral angles ψ against φ of amino acid residues in protein structure. The figure on the left illustrates the definition of the φ and ψ backbone dihedral angles. The ω angle at the peptide bond is normally 180°, since the partial-double-bond character keeps the peptide bond planar. The figure in the top right shows the allowed φ,ψ backbone conformational regions from the Ramachandran et al. 1963 and 1968 hard-sphere calculations: full radius in solid outline, reduced radius in dashed, and relaxed tau (N-Cα-C) angle in dotted lines. Because dihedral angle values are circular and 0° is the same as 360°, the edges of the Ramachandran plot "wrap" right-to-left and bottom-to-top. For instance, the small strip of allowed values along the lower-left edge of the plot are a continuation of the large, extended-chain region at upper left.

<span class="mw-page-title-main">Frederic M. Richards</span> American biochemist and biophysicist (1925–2009)

Frederic Middlebrook Richards, commonly referred to as Fred Richards, was an American biochemist and biophysicist known for solving the pioneering crystal structure of the ribonuclease S enzyme in 1967 and for defining the concept of solvent-accessible surface. He contributed many key experimental and theoretical results and developed new methods, garnering over 20,000 journal citations in several quite distinct research areas. In addition to the protein crystallography and biochemistry of ribonuclease S, these included solvent accessibility and internal packing of proteins, the first side-chain rotamer library, high-pressure crystallography, new types of chemical tags such as biotin/avidin, the nuclear magnetic resonance (NMR) chemical shift index, and structural and biophysical characterization of the effects of mutations.

The global distance test (GDT), also written as GDT_TS to represent "total score", is a measure of similarity between two protein structures with known amino acid correspondences but different tertiary structures. It is most commonly used to compare the results of protein structure prediction to the experimentally determined structure as measured by X-ray crystallography, protein NMR, or, increasingly, cryoelectron microscopy. The metric was developed by Adam Zemla at Lawrence Livermore National Laboratory and originally implemented in the Local-Global Alignment (LGA) program. It is intended as a more accurate measurement than the common root-mean-square deviation (RMSD) metric - which is sensitive to outlier regions created, for example, by poor modeling of individual loop regions in a structure that is otherwise reasonably accurate. The conventional GDT_TS score is computed over the alpha carbon atoms and is reported as a percentage, ranging from 0 to 100. In general, the higher the GDT_TS score, the more closely a model approximates a given reference structure.

<span class="mw-page-title-main">Molecular biophysics</span> Interdisciplinary research area

Molecular biophysics is a rapidly evolving interdisciplinary area of research that combines concepts in physics, chemistry, engineering, mathematics and biology. It seeks to understand biomolecular systems and explain biological function in terms of molecular structure, structural organization, and dynamic behaviour at various levels of complexity. This discipline covers topics such as the measurement of molecular forces, molecular associations, allosteric interactions, Brownian motion, and cable theory. Additional areas of study can be found on Outline of Biophysics. The discipline has required development of specialized equipment and procedures capable of imaging and manipulating minute living structures, as well as novel experimental approaches.

<span class="mw-page-title-main">Janet Thornton</span> British bioinformatician and academic

Dame Janet Maureen Thornton, is a senior scientist and director emeritus at the European Bioinformatics Institute (EBI), part of the European Molecular Biology Laboratory (EMBL). She is one of the world's leading researchers in structural bioinformatics, using computational methods to understand protein structure and function. She served as director of the EBI from October 2001 to June 2015, and played a key role in ELIXIR.

Yizhi Jane Tao is a Chinese biochemist, structural biologist, and professor of biochemistry and cell biology at Rice University in Houston, Texas. Professor Tao led a team of researchers to be the first to map the structure of the influenza A virus nucleoprotein to an atomic level, a feat which circulated widely in the popular press. She was named among the top ten most influential Chinese of 2006 by a consortium of China's leading media outlets including Phoenix Satellite Television, China News Service, Asia Newsweek, and World Journal.

<span class="mw-page-title-main">DNA polymerase beta</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">Protein dynamics</span>

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<span class="mw-page-title-main">Structure validation</span> Process of evaluating 3-dimensional atomic models of biomacromolecules

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Resolution by Proxy (ResProx) is a method for assessing the equivalent X-ray resolution of NMR-derived protein structures. ResProx calculates resolution from coordinate data rather than from electron density or other experimental inputs. This makes it possible to calculate the resolution of a structure regardless of how it was solved. ResProx was originally designed to serve as a simple, single-number evaluation that allows straightforward comparison between the quality/resolution of X-ray structures and the quality of a given NMR structure. However, it can also be used to assess the reliability of an experimentally reported X-ray structure resolution, to evaluate protein structures solved by unconventional or hybrid means and to identify fraudulent structures deposited in the PDB. ResProx incorporates more than 25 different structural features to determine a single resolution-like value. ResProx values are reported in Angstroms. Tests on thousands of X-ray structures show that ResProx values match very closely to resolution values reported by X-ray crystallographers. Resolution-by-proxy values can be calculated for newly determined protein structures using a freely accessible ResProx web server. This server accepts protein coordinate data and generates a resolution estimate for that input structure.

<span class="mw-page-title-main">Randy Read</span> Canadian-British scientist (1957–)

Randy John Read is a Wellcome Trust Principal Research Fellow and professor of protein crystallography at the University of Cambridge.

<span class="mw-page-title-main">Complementarity plot</span>

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<span class="mw-page-title-main">Barbara Low (biochemist)</span> American biochemist and biophysicist (1920–2019)

Barbara Wharton Low was a biochemist, biophysicist, and a researcher involved in discovering the structure of penicillin and the characteristics of other antibiotics. Her early work at Oxford University with Dorothy Hodgkin used X-ray crystallography to confirm the molecular structure of penicillin, which at the time was the largest molecule whose structure has been determined using that method. Later graduate work saw her study with Linus Pauling and Edwin Cohn before becoming a professor in her own right. Low's laboratory would accomplish the discovery of the pi helix, investigate the structure of insulin, and conduct research into neurotoxins.

Bonnie Ann Wallace, FRSC is a British and American biophysicist and biochemist. She is a professor of molecular biophysics in the department of biological sciences, formerly the department of crystallography, at Birkbeck College, University of London, U.K.

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Further reading