November 8, 2012
Scientists at the IPD describe a set of “rules” for the design of proteins from scratch in the latest issue of Nature.
Proteins are an enormous molecular achievement: chains of amino acids that fold spontaneously into a precise conformation, time after time, optimized by evolution for their particular function. Yet given the exponential number of contortions possible for any chain of amino acids, dictating a sequence that will fold into a predictable structure has been a daunting task.
Now researchers report that they can do just that. By following a set of rules described in a paper published in Nature today1, a team from David Baker’s laboratory at the University of Washington in Seattle has designed five proteins from scratch that fold reliably into predicted conformations. In a blind test, the team showed that the synthesized proteins closely match the predicted structures.
One might wonder how designing a new protein from scratch could be better than starting with natural proteins, given the head start that nature has in evolving effective functions and stable conformations. In fact, evolution has honed the structures of many proteins so precisely that it can be difficult to get the backbone to budge into another conformation to accommodate a new function, Baker says. “This paper provides the opportunity to design the structure and function at the same time,” says Baker. “Rather than taking an already existing scaffold, now you can design a backbone to order for exactly the function you want to carry out.” That will be the next step — incorporating function into the designs.
Read the full article here.
September 4, 2012
The Institute for Protein Design and David Baker’s laboratory move into the new Molecular Engineering & Sciences building located in the heart of the University of Washington campus. Read about the Institute’s new home and its exciting research in the Seattle Times.
The four-story, $77 million Molecular Engineering & Sciences building opened this month, just south of Gerberding Hall. And unlike old labs of the past, which tended to be dark and isolating, this one is filled with sunlight and designed with collaborative spaces for scientists to work together across a range of disciplines….
…Biochemistry professor David Baker gestured to researchers lined up in a row of desks, working on computers to design proteins that could help treat Ebola, Hodgkins Lymphoma and AIDS.
Baker said the most promising discoveries are licensed to private companies to carry on the research and find out if the proteins really do what researchers thought they would do. “We do simple things, then license the results to a pharmaceutical company,” he said.
Of those 400 proteins being investigated each month, about 25 to 50 a month are inspired by an unusual source: Online gamers playing Foldit, a free protein-folding game (www.fold.it), that was developed in collaboration between the UW’s molecular biology department and the UW’s Center for Game Science, Baker said.
About 230,000 players worldwide have downloaded the game, and use intuition and spatial reasoning to try to design proteins with stable, efficient designs.
Another contribution to unraveling protein structures comes from the more than 300,000 people who have downloaded a UW-designed program — Rosetta@home — which works kind of like a screen saver, taking advantage of processing time on idle computers. It, too, tries to work out the three-dimensional profile of proteins.
June 10, 2012
As reported in the latest issue of Nature Biotechnology, David Baker and scientists at the IPD publish exciting new methods to improve the potency and breadth of computer-designed protein inhibitors of influenza.
The ability to engineer structures of protein complexes and to design interactions of high affinity and specificity would have countless applications in biology, medicine and public health. With the advent of next-generation sequencing, this long-standing goal may now be within reach. Exciting new methods that combine sequencing with techniques for protein display and selection allow the functional properties of hundred of thousands of mutants to be measured simultaneously. Also called ‘deep mutational scanning’, this approach is exploited in a milestone study in this issue by Baker and colleagues to optimize the binding properties of two computationally designed protein inhibitors of H1N1 influenza hemagglutinin.
Read the entire article here.
April 13, 2012
Dr. Paul Ramsey, CEO of UW Medicine, announces the establishment of the Institute for Protein Design:
A major challenge for designing proteins for specific purposes is predicting three-dimensional shape from the amino acid sequence. David Baker, UW professor of biochemistry and an investigator of the Howard Hughes Medical Institute, has had remarkable success in making these predictions and in designing new proteins with new functions. Dr. Baker will serve as the institute’s director. His work includes the development of Rosetta software, which has become the world’s standard for predicting protein structures and designing new proteins. His regular success with the protein structure prediction experiment (CASP) and his numerous awards for protein design breakthroughs attest to his international stature in the fields of protein structure prediction and protein design. His group has used Rosetta to design proteins with a wide range of new functions, including catalysts for chemical reactions, HIV vaccine candidates, and flu virus inhibitors, and involved the general public in these efforts through Rosetta@home.
The Institute for Protein Design will coalesce and expand existing strengths within the UW and Seattle. The institute will integrate UW expertise in biochemistry, engineering, computer science and medicine, and leverage local strength in the software industry to solve problems in medicine.Together they will pursue new pathways to solving medical challenges by using and enhancing already successful strategies that Dr. Baker and his colleagues have developed.
See full press release.