Protein Design Institute: Rosetta & Collaborative Research

The Protein Design Institute, also known as the Institute for Protein Design (IPD), was established by the University of Washington in 2012, and has since been revolutionising the process of synthetic protein development. The Institute aims to effectively solve ongoing problems related to synthetic protein development by serving as a platform for UW experts in various disciplines to collaborate.

Protein Design Institute

Protein Design Institute

Protein Design Institute

Protein Design Institute

The use of synthetic proteins is widespread in multiple research fields, however the process of designing and developing novel, useful synthetic proteins remains extremely difficult and time-consuming. The Institute for Protein Design (IPD) was founded with the aim of improving the process of synthetic protein design and development, enabling researchers to create synthetic proteins far more easily. [1]

Protein Folding Problem

Protein Folding Problem

Protein Folding Problem

Protein Folding Problem

The most significant hurdle when designing synthetic proteins has long been an issue referred to as the ‘protein folding problem.’ The problem describes the difficulty of predicting three-dimensional protein structures from amino acid sequences. This difficulty means that, when designing a synthetic protein, it is often not possible to predict what structure and function the final product will have.

David Baker, Director of the IPD at UW {Photo Credit: IPD UW, Seattle}

Fortunately, the IPD has made considerable progress towards solving the problem; Dr Baker, director of the Institute, (pictured left) has developed a computer program termed Rosetta, which enables researchers to predict structures of real or hypothetical proteins using only the amino acid sequence.

Traditional structural prediction techniques work by comparing an amino acid sequence of interest to the amino acid sequences of a vast library of solved protein structures, and then generating potential structures based upon amino acid sequence similarities (a process called ‘homology modelling’). Rosetta, however, uses a technique termed ‘ab initio modelling’, which predicts structure by considering the interactions between neighbouring amino acids.

The principle weakness of homology modelling is its reliance upon vast libraries of solved protein structures. Solving protein structures experimentally is expensive, difficult and time-consuming, and libraries of solved protein structures are therefore very incomplete, which significantly limits the effectiveness of homology modelling. A strength of Rosetta is that it doesn’t rely on the existence of these vast libraries.

Dr. Paul Ramsey, Dean of the University of Washington School of Medicine, has referred to Dr Baker’s development of Rosetta as a “remarkable success”, whilst press coverage of Dr Baker’s work claims he has “all but solved one of the biggest challenges in modern science”, referring to the protein folding problem. [2] [3]

Professor John Moult, head of the Critical Assessment of protein Structure Prediction (CASP) claims the progress made at the Institute is “going to be totally revolutionary” and is the “breakthrough” he and others have “been waiting 10 years for.” [3]


The Rosetta@home/BOINC workflow

1. IPD researchers who submit designed protein sequences in the queue for computing jobs managed by [email protected] servers.


The Rosetta@home/BOINC workflow

2. [email protected] servers then sends jobs out to volunteer computers to process.


The Rosetta@home/BOINC workflow

3. Once the completed work unit is returned (by BOINC), researchers download structures from the [email protected] servers.


The Rosetta@home/BOINC workflow

4. Designs with the lowest energy conformations that are structurally identical to the design are subsequently tested in the lab. Once the designs have been tested, a new round of improved designs are calculated and new tasks are sent to the volunteer computer to go through the same cycle.


Illustration 2. The [email protected]/BOINC workflow

Synthetic Proteins

Synthetic Proteins

Synthetic Proteins

Synthetic Proteins

Synthetic proteins already designed using the Rosetta software include candidates for HIV and respiratory syncytial virus (RSV) vaccines, successful flu virus inhibitors, and, outside of medical research, enzymes that can promote the removal of carbon dioxide from the atmosphere, providing a potential tool to combat environmental climate change. It is predicted that through the continued use and improvement of Rosetta, the software will have an increasingly significant and far-reaching impact on medical science. [1] [2]

MMRF Pledge

MMRF Pledge

MMRF Pledge

MMRF Pledge

Recognising the importance of the work being conducted at the IPD, the Michelson Medical Research Foundation earlier this year pledged a gift of between $100,000 and $250,000. The Institute explains that investments in their work, such as the contribution pledged by the Michelson Medical Research Foundation, serve to “allow the IPD to scale up its research” and reduce the time taken to “turn a concept into a real-world solution.” [4]

Protein Design Institute | Molecular Engineering & Sciences Building [University of Washington]

Illustration 3. 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.

Image Credit

  • (Featured Image) Drug Target from X-ray study reveals long-sought insights into potential drug target [2017. phys.org]
  • (Illustration #1) [email protected] BIONIC from BIONIC Open-source software for volunteer computing [2017. Berkley.edu]
  • (Illustration #2) 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]

Christopher Edward Jones is a biochemist and writer currently affiliated with Queen Mary University of London, where he is part of a research group focusing on the restriction factors of HIV. In the past he has worked with multiple biomedical research groups in both industry and academia. He has a research interest in the biochemical mechanisms of virus restriction and a general interest in all areas of science.

Christopher Edward Jones is a biochemist and writer currently affiliated with Queen Mary University of London, where he is part of a research group focusing on the restriction factors of HIV. In the past he has worked with multiple biomedical research groups in both industry and academia. He has a research interest in the biochemical mechanisms of virus restriction and a general interest in all areas of science.

Christopher Edward Jones is a biochemist and writer currently affiliated with Queen Mary University of London, where he is part of a research group focusing on the restriction factors of HIV. In the past he has worked with multiple biomedical research groups in both industry and academia. He has a research interest in the biochemical mechanisms of virus restriction and a general interest in all areas of science.

Christopher Edward Jones is a biochemist and writer currently affiliated with Queen Mary University of London, where he is part of a research group focusing on the restriction factors of HIV. In the past he has worked with multiple biomedical research groups in both industry and academia. He has a research interest in the biochemical mechanisms of virus restriction and a general interest in all areas of science.


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.