...Changing The World

Institute for Protein Design [UW].

Project Description

Grantee Year Issue Initiative
Institute for Protein Design [IPD] at University of Washington [UW] 2017 Proteins solve the challenges faced during evolution, but the proteins which exist today took billions of years to evolve to this state. The goal of Protein Design is to create new “synthetic” proteins which can help solve the problems we face now in modern times. The Protein Design Initiative

Grantee Institute for Protein Design [IPD] at University of Washington [UW]
Year Issue Initiative
2017 Proteins solve the challenges faced during evolution, but the proteins which exist today took billions of years to evolve to this state. The goal of Protein Design is to create new “synthetic” proteins which can help solve the problems we face now in modern times. The Protein Design Initiative

Grantee Institute for Protein Design [IPD] at University of Washington [UW]
Year Issue Initiative
2017 Institute for Protein Design at the University of Washington Protein Design Initiative

Grantee Institute for Protein Design [IPD] at University of Washington [UW]
Year Issue Initiative
2017 Proteins solve the challenges faced during evolution, but the proteins which exist today took billions of years to evolve to this state. The goal of Protein Design is to create new “synthetic” proteins which can help solve the problems we face now in modern times. The Protein Design Initiative

The Michelson Medical Research Foundation and its founder, Dr. Gary K. Michelson, are strong advocates of the biotech approach toward medicine. In addition of its commitment toward the USC Michelson Center for Convergent Bioscience, Dr. Michelson has become, since May 2017, a designated benefactor of the Institute for Protein Design [IPD], headed by Dr. David Baker, Ph.D and located at the University of Washington [UW].

The Protein Design Initiative

The Protein Design Initiative

The Protein Design Initiative

The Protein Design Initiative

The functions of naturally occurring proteins solve the challenges faced during evolution. Proteins are adaptive and can change their function in response to changing selection pressures. The proteins which exist today took billions of years to evolve to this state. The goal of Protein Design is to create new “synthetic” proteins from scratch which can help solve modern day problems.

This initiative will improve research services and provide additional resources towards further development of protein design capabilities. The newly formed partnership has already helped to inspire and expand donations coming into the school.

The Institute for Protein Design [IPD]

The Institute for Protein Design [IPD]

The Institute for Protein Design [IPD]

The Institute for Protein Design [IPD]

The Institute for Protein Design [IPD] is located within the University of Washington [UW] and was established in 2012 with a singular focus to advance the potential of designing proteins. It requires high-level expertise and talent in computing and software, biochemistry, genome sciences, biological structure, pharmacology, immunology and other basic science disciplines, as well as clinical medicine.

University of Washington, MolES and NanoES Buildings (Seattle, WA) ZGF Architects designed the two-phased MolES and NanoES Buildings, which provide 160,000 SF of critical research space in the field of interdisciplinary molecular engineering considered critical for ensuring future economic, environmental and medical health worldwide. Sited within the campus core, the buildings were designed to fit within the historic context while also reflecting the cutting-edge nature of the research housed within them.

Over the past 16 years, UW researchers have made significant progress in protein design and protein structure prediction, developing the world leading Rosetta software. During this period, UW scientists have developed methods for designing proteins with a wide range of new functions, including catalysts for chemical reactions, HIV and RSV vaccine candidates, and flu virus inhibitors. The IPD integrates these strengths with experts in biochemistry, engineering, computer science and medicine, and leverages the strength of the software industry. [1]

Proteins Explained

Proteins Explained

Proteins Explained

Proteins Explained

Proteins are large, complex molecules that play many critical roles in the body. They do most of the work in cells and are required for the structure, function, and regulation of the body’s tissues and organs. Proteins are made up of hundreds or thousands of smaller units called amino acids, which are attached to one another in long chains. There are 20 different types of amino acids that can be combined to make a protein. The sequence of amino acids determines each protein’s unique 3-dimensional structure and its specific function.

The structure and dynamic behavior dictate the function of the molecule. Proteins can be described according to their range of functions, as described in the table below. [2]

Function Description Example
Antibody Antibodies bind to specific foreign particles, such as viruses and bacteria, to help protect the body. Immunoglobulin G (IgG)
Enzyme Enzymes carry out almost all of the thousands of chemical reactions that take place in cells. They also assist with the formation of new molecules by reading the genetic information stored in DNA. Phenylalanine hydroxylase
Messenger Messenger proteins, such as some types of hormones, transmit signals to coordinate biological processes between different cells, tissues, and organs. Growth hormone
Structural component These proteins provide structure and support for cells. On a larger scale, they also allow the body to move. Actin
Transport/Storage These proteins bind and carry atoms and small molecules within cells and throughout the body. Ferritin

The Importance of Designing Proteins

The Importance of Designing Proteins

The Importance of Designing Proteins

The Importance of Designing Proteins

Functions of naturally occurring proteins solve the challenges faced during evolution. They are adaptive and can change their function in response to changing selection pressures. The proteins which exist today took billions of years to evolve to this state. The goal of Protein Design is to create new “synthetic” proteins from scratch which can help solve modern day problems.

Design Problems

Design Problems

Design Problems
Design Problems
  • Not to be confused with protein prediction, this protein design initiative focuses solely on the development of new synthetic protein structures
  • It starts with the new synthetic structure of a potential protein which is desired, and then works backwards to find the corresponding amino acid sequence which would fold into that structure
  • It is a “one to many” approach using one completed structure to predict which amino acid sequence will fold into that structure [3]

The Design Process

The Design Process

The Design Process

The Design Process

  1. Computer model calculates the optimal sequence for desired structure or function
  2. Labs can create (or buy) the synthetic piece of DNA to encode this protein
  3. The newly created synthetic protein is further tested and evaluated for application

Crowd Sourcing Protein Design

Crowd Sourcing Protein Design

Crowd Sourcing Protein Design

Crowd Sourcing Protein Design

Designing proteins requires complex computations and enough server space to process those computations. There are an astronomical number (~3 Nres) of polypeptide chain conformations and (20 Nres) protein sequences that make up a protein. In order to keep up with the magnitude of computations needed, two crowdsourcing solutions arose.

David Baker, Director of the IPD at UW: “Those distinctions between scientist and the public… are a little bit artificial…really anyone who is interested can participate in scientific research.”

Rosetta@home uses idle computer processing resources from volunteers' computers to perform calculations for protein design at UW. Screenshot is from the "Elite Dangerous players", an international community team {Credit: IPD University of Washington, Seattle}

[email protected] uses idle computer processing resources from volunteers’ computers to perform calculations on individual work-units. Completed results are sent to a central project server where they are validated and assimilated into project databases. The project is cross-platform, and runs on a wide variety of hardware configurations. Users can view the progress of their individual protein structure prediction on the [email protected] screensaver. [4]

This screensaver is how some users of [email protected] noticed inefficiency in the way computer algorithm folds proteins. Feedback was provided to suggest they could help improve the efficiency of the process if they could interact with it manually. A new experimental game, Foldit, was born which allowed them to do so. 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. [5]

Foldit

Foldit

Foldit

Foldit

Researchers at UW discussing Foldit: Humans use a much more varied range of exploration methods than computers. Different players use different move sequences, both according to the puzzle type and throughout the duration of a puzzle.”

David Baker, Director of the Institute for IPD at UW describing "FoldIt" game designs {Credit: IPD University of Washington, Seattle}

Foldit is an online puzzle video game about protein folding developed in response to this feedback from [email protected] users. It is part of an experimental research project developed by the UW, 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 well 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 (native state) that can be applied to relevant proteins in the real world. [6]

Protein Design Initiative: University of Washington, MolES and NanoES BuildingsProtein Design Initiative: University of Washington, MolES and NanoES Buildings – ZGF programmed and designed the two-phased MolES and NanoES Buildings, which together provide 160,000 SF of critical research space in the field of interdisciplinary molecular engineering considered critical for ensuring future economic, environmental and medical health worldwide. {Photo Credit: ZGF Architects}

Protein Design Initiative: University of Washington, MolES and NanoES BuildingsProtein Design Initiative: University of Washington, MolES and NanoES Buildings – Sited within the campus core, the buildings were designed to fit within the historic context while also reflecting the cutting-edge nature of the research housed within them. {Photo Credit: ZGF Architects}

Image Credit

  • (Featured Image) The Molecular Engineering & Sciences building, home to the Molecular Engineering & Sciences Institute, Molecular Analysis Facility, and Clean Energy Institute, is a 90,300-square-foot space near the center of campus. The building, designed by Zimmer Gunsul Frasca Architects, features state-of-the-art labs, innovative common spaces that encourage collaboration, and cutting-edge green features. The building embodies the interdisciplinary nature of molecular engineering. Each of the $77 million building’s four floors consists of a large, open laboratory and an office area. These labs are shared by three to five PIs, their students, postdocs and lab technicians. All lab elements—benches, shelving, even instruments—are reconfigurable as needs and researchers change. The basement features the largest vibration-free laboratory on the West Coast, along with instruments that minimize electromagnetic interference. from UWA – Molecular Engineering Project [2017. AEI Affiliated Engineers]
  • (Fig.I) [email protected] uses idle computer processing resources from volunteers’ computers to perform calculations for protein design at UW. Screenshot is from the “Elite Dangerous players”, an international community team from [2015. IPD. The University of Washington, Seattle]
  • (Fig.II) Foldit is an online puzzle video game created at UW about protein folding. Designs from users could potentially be applied to relevant proteins in the real world {Credit: IPD University of Washington, Seattle}” alt=”Foldit is an online puzzle video game created at UW about protein folding. Designs from users could potentially be applied to relevant proteins in the real world from [2015. IPD. The University of Washington, Seattle]
  • (Fig.III) The University of Washington, MolES and NanoES Buildings Seattle, WA from [2017. ZGF Architecture]
  • (Fig.IV) David Baker, Director of the IPD at UW from [2015. IPD. The University of Washington, Seattle]
  • (Fig.V) The University of Washington, MolES and NanoES Buildings Seattle, WA from [2017. ZGF Architecture]
  • (Fig.VI) David Baker, Director of the Institute for IPD at UW describing “FoldIt” game designs from [2015. IPD. The University of Washington, Seattle]
Gary Karlin Michelson, M.D. and Alya Michelson from the Michelson Medical Research Foundation are proud benefactors of the Institute for Protein Design at the University of Washington. Their generous support advances cutting edge research towards a revolutionary protein design pipeline.

Gary Karlin Michelson, M.D. and Alya Michelson from the Michelson Medical Research Foundation are proud benefactors of the Institute for Protein Design at the University of Washington. Their generous support advances cutting edge research towards a revolutionary protein design pipeline.

Gary Karlin Michelson, M.D. and Alya Michelson from the Michelson Medical Research Foundation are proud benefactors of the Institute for Protein Design at the University of Washington. Their generous support advances cutting edge research towards a revolutionary protein design pipeline.

Gary Karlin Michelson, M.D. and Alya Michelson from the Michelson Medical Research Foundation are proud benefactors of the Institute for Protein Design at the University of Washington. Their generous support advances cutting edge research towards a revolutionary protein design pipeline.

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