David Baker | |
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Born | October 6, 1962 |
Alma mater | |
Known for | |
Spouse | Hannele Ruohola-Baker |
Awards |
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Scientific career | |
Fields | Computational biology |
Institutions | |
Doctoral advisor | Randy Schekman |
Other academic advisors | David Agard |
Doctoral students | Richard Bonneau |
Other notable students | Brian Kuhlman, Tanja Kortemme |
Website | www |
David Baker (born October 6, 1962, in Seattle, Washington [3] ) is an American biochemist and computational biologist who has pioneered methods to predict and design the three-dimensional structures of proteins. He is the Henrietta and Aubrey Davis Endowed Professor in Biochemistry and an adjunct professor of genome sciences, bioengineering, chemical engineering, computer science, and physics at the University of Washington. He serves as the director of the Rosetta Commons, a consortium of labs and researchers that develop biomolecular structure prediction and design software. The problem of protein structure prediction to which Baker has contributed significantly has now been largely solved by DeepMind using artificial intelligence. [4] Baker is a Howard Hughes Medical Institute investigator and a member of the United States National Academy of Sciences. He is also the director of the University of Washington's Institute for Protein Design. [5]
Baker did his graduate work in biochemistry at the University of California, Berkeley in the laboratory of Randy Schekman, where he worked predominantly on protein transport and trafficking in yeast. He did his postdoctoral work with David Agard of University of California, San Francisco.
For his work on protein folding, Baker received the 2008 Sackler International Prize in Biophysics, [6] the 2021 Breakthrough Prize in Life Sciences, [7] and in 2022 the Wiley Prize. [8] For 2022 he was awarded the BBVA Foundation Frontiers of Knowledge Award in the category "Biology and Biomedicine". [9]
Baker was elected a Fellow of the American Academy of Arts and Sciences in 2009. [10] He is married to Hannele Ruohola-Baker, another biochemist at UW. They have two children.
Baker's group developed the Rosetta algorithm for ab initio protein structure prediction, which has been extended to a distributed computing project called Rosetta@Home [11] [12] and Foldit. [13] [14] The project aims to produce structural models for protein complexes as well as individual polypeptide chains. The group specializes in the CASP structure prediction experiment using ab initio methods, including both manually assisted and automated variants of the Rosetta protocol. [15] [16]
Members of his group are active in the field of protein design; [17] they are noted for designing a protein, known as Top7, with an entirely novel fold. [18]
Although primarily known for the development of methods for computational prediction of protein structure and function, he is also interested in the use of computational methods to drive experimental assessment of biology; his laboratory maintains an active experimental biochemistry group. He also served on the Life Sciences jury for the Infosys Prize in 2016.
In December 2018, Baker spoke at the "Antibody Engineering and Therapeutics" conference in San Diego, California. [19]
In April 2019, Baker gave a TED talk titled "5 challenges we could solve by designing new proteins" at TED2019 in Vancouver, Canada. [20]
Structural biology is a field that is many centuries old which, as defined by the Journal of Structural Biology, deals with structural analysis of living material at every level of organization. Early structural biologists throughout the 19th and early 20th centuries were primarily only able to study structures to the limit of the naked eye's visual acuity and through magnifying glasses and light microscopes.
Protein folding is the physical process in which a polypeptide is synthesized by a ribosome from an unstable, random coil into a linear chain of amino acids, resulting in protein's three-dimensional structure. This is typically a 'folded' conformation, by which the protein becomes biologically functional.
Structural genomics seeks to describe the 3-dimensional structure of every protein encoded by a given genome. This genome-based approach allows for a high-throughput method of structure determination by a combination of experimental and modeling approaches. The principal difference between structural genomics and traditional structural prediction is that structural genomics attempts to determine the structure of every protein encoded by the genome, rather than focusing on one particular protein. With full-genome sequences available, structure prediction can be done more quickly through a combination of experimental and modeling approaches, especially because the availability of large number of sequenced genomes and previously solved protein structures allows scientists to model protein structure on the structures of previously solved homologs.
Protein structure prediction is the inference of the three-dimensional structure of a protein from its amino acid sequence—that is, the prediction of its secondary and tertiary structure from primary structure. Structure prediction is different from the inverse problem of protein design. Protein structure prediction is one of the most important goals pursued by computational biology; and it is important in medicine and biotechnology.
Top7 is an artificial protein, classified as a de novo protein. This means that the protein itself was designed to have a specific structure and functional properties.
Protein design is the rational design of new protein molecules to design novel activity, behavior, or purpose, and to advance basic understanding of protein function. Proteins can be designed from scratch or by making calculated variants of a known protein structure and its sequence. Rational protein design approaches make protein-sequence predictions that will fold to specific structures. These predicted sequences can then be validated experimentally through methods such as peptide synthesis, site-directed mutagenesis, or artificial gene synthesis.
Rosetta@home is a volunteer computing project researching protein structure prediction on the Berkeley Open Infrastructure for Network Computing (BOINC) platform, run by the Baker lab. Rosetta@home aims to predict protein–protein docking and design new proteins with the help of about fifty-five thousand active volunteered computers processing at over 487,946 GigaFLOPS on average as of September 19, 2020. Foldit, a Rosetta@home videogame, aims to reach these goals with a crowdsourcing approach. Though much of the project is oriented toward basic research to improve the accuracy and robustness of proteomics methods, Rosetta@home also does applied research on malaria, Alzheimer's disease, and other pathologies.
Michael Levitt, is a South African-born biophysicist and a professor of structural biology at Stanford University, a position he has held since 1987. Levitt received the 2013 Nobel Prize in Chemistry, together with Martin Karplus and Arieh Warshel, for "the development of multiscale models for complex chemical systems". In 2018, Levitt was a founding co-editor of the Annual Review of Biomedical Data Science.
The TIM barrel, also known as an alpha/beta barrel, is a conserved protein fold consisting of eight alpha helices (α-helices) and eight parallel beta strands (β-strands) that alternate along the peptide backbone. The structure is named after triose-phosphate isomerase, a conserved metabolic enzyme. TIM barrels are ubiquitous, with approximately 10% of all enzymes adopting this fold. Further, five of seven enzyme commission (EC) enzyme classes include TIM barrel proteins. The TIM barrel fold is evolutionarily ancient, with many of its members possessing little similarity today, instead falling within the twilight zone of sequence similarity.
David S. Eisenberg is an American biochemist and biophysicist best known for his contributions to structural biology and computational molecular biology. He has been a professor at the University of California, Los Angeles since the early 1970s and was director of the UCLA-DOE Institute for Genomics & Proteomics, as well as a member of the California NanoSystems Institute (CNSI) at UCLA.
In computational biology, de novo protein structure prediction refers to an algorithmic process by which protein tertiary structure is predicted from its amino acid primary sequence. The problem itself has occupied leading scientists for decades while still remaining unsolved. According to Science, the problem remains one of the top 125 outstanding issues in modern science. At present, some of the most successful methods have a reasonable probability of predicting the folds of small, single-domain proteins within 1.5 angstroms over the entire structure.
Foldit is an online puzzle video game about protein folding. It is part of an experimental research project developed by the University of Washington, Center for Game Science, in collaboration with the UW Department of Biochemistry. The objective of Foldit is to fold the structures of selected proteins as perfectly as possible, using tools provided in the game. The highest scoring solutions are analyzed by researchers, who determine whether or not there is a native structural configuration that can be applied to relevant proteins in the real world. Scientists can then use these solutions to target and eradicate diseases and create biological innovations. A 2010 paper in the science journal Nature credited Foldit's 57,000 players with providing useful results that matched or outperformed algorithmically computed solutions.
Victor Muñoz is a biochemist whose focus has been on protein folding and design. He provided experimental evidence for a mechanism of protein folding called as "downhill folding". He has pioneered various computational and experimental techniques to study this mechanism as well as to gain insights into the general process of protein folding.
David Tudor Jones is a Professor of Bioinformatics, and Head of Bioinformatics Group in the University College London. He is also the director in Bloomsbury Center for Bioinformatics, which is a joint Research Centre between UCL and Birkbeck, University of London and which also provides bioinformatics training and support services to biomedical researchers. In 2013, he is a member of editorial boards for PLoS ONE, BioData Mining, Advanced Bioinformatics, Chemical Biology & Drug Design, and Protein: Structure, Function and Bioinformatics.
Martin Gruebele is a German-born American physical chemist and biophysicist who is currently James R. Eiszner Professor of Chemistry, Professor of Physics, Professor of Biophysics and Computational Biology at the University of Illinois Urbana-Champaign, where he is the principal investigator of the Gruebele Group.
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/.
CS23D is a web server to generate 3D structural models from NMR chemical shifts. CS23D combines maximal fragment assembly with chemical shift threading, de novo structure generation, chemical shift-based torsion angle prediction, and chemical shift refinement. CS23D makes use of RefDB and ShiftX.
Tamir Gonen is an American structural biochemist and membrane biophysicist best known for his contributions to structural biology of membrane proteins, membrane biochemistry and electron cryo-microscopy (cryoEM) particularly in electron crystallography of 2D crystals and for the development of 3D electron crystallography from microscopic crystals known as MicroED. Gonen is an Investigator of the Howard Hughes Medical Institute, a professor at the University of California, Los Angeles, the founding director of the MicroED Imaging Center at UCLA and a Member of the Royal Society of New Zealand.
Jens Meiler is a German-American biologist and structural chemist. He currently serves as a Professor of Chemistry and Associate Professor of Pharmacology and Biomedical Informatics at Vanderbilt University. His research focuses on protein structures and computational biology, drawing on interdisciplinary techniques from other sciences.
Derek Dek Woolfson is a British chemist and biochemist. He is a professor of chemistry and biochemistry. and director of the Bristol BioDesign Institute at the University of Bristol, and founder of synthetic biology spin-out company Rosa Biotech.