Session B2
6067
Disclaimer — This paper partially fulfills a writing requirement for first year (freshman) engineering students at the
University of Pittsburgh Swanson School of Engineering. This paper is a student, not a professional , paper. This paper is based on publicly available information and may not be provide complete analyses of all relevant data. If this paper is used for any purpose other than these authors’ partial fulfillment of a writing requirement for first year (freshman) engineering students at the University of Pittsburgh Swanson School of Engineering, the user does so at his or her own risk.
Tylar Farmer, Tsf13@pitt.edu, Bursic 2:00, Patrick Bohse, Pab120@pitt.edu, Mahboobin 10:00
Revised Proposal — Two popular methods exist when engineering a protein: directed evolution and rational design.
Directed evolution utilizes a controlled environment to create proteins through induced mutations and selection. Rational design makes desired changes to a protein by directly manipulating its amino acids, creating a protein to serve a specific purpose. Directed evolution is currently more commonly used, since rational design relies on structural knowledge of the protein of interest, which is often unknown.
Even when this information is available, a method of predicating how exactly a protein will fold after inducing changes has not yet been discovered. Crowdsourcing manpower and computational power in order to improve current protein depictions can lead to manipulation of proteins via rational design.
Two free programs, “Folding@home and “Foldit”, allow anyone with a computer and internet access to contribute to protein engineering by volunteering their mind or computational power to help solve protein folding patterns.
Folding@home takes the unused processing power of a user’s computer and repeatedly runs calculations to find a more stable from of that protein. Foldit, however, presents the protein directly to the user and assigns a “score” based on how stable the protein is [1].
Rational design has allowed protein engineers to create artificial proteins, such as an altered form of glutathione transferase, which, when compared to the unaltered form demonstrated increased metabolism. This can be applied to the treatment of digestive disorders and research regarding enzyme activity in a living system [2].
There are ethical issues that must be dealt with in protein engineering, such as whether or not it is acceptable to alter the human genome using engineered proteins or if these proteins are even safe for use on humans [3].
Sources to be consulted include, the Foldit and
Folding@home websites and the RCSB’s Protein Data Bank.
The Foldit and Folding@home websites will provide information on developments and breakthroughs in folding design, while the RCSBPDB will provide all known information on any protein in nature. Additional valuable sources include the National Center for Biotechnology
Information and ScienceDirect, as both have provided us with articles relevant to protein design and information about
University of Pittsburgh Swanson School of Engineering
Submission Date: 2016/01/29
1 current issues in protein engineering, such as how to create proteins that can correct genetic defects [2]. These sources will provide us with the information necessary to analyze the significance of rational design in protein engineering through crowdsourcing.
Our paper will begin with a description of rational design and directed evolution along with an explanation of the issues facing rational design. We will later discuss two programs that are working to resolve said issues,
Folding@home and Foldit. We will then talk about applications of protein engineering and the social and ethical repercussions that come along with it.
[1] “The Science behind Foldit.” (2015). Fold.it. (website). https://fold.it/portal/info/about
[2] K. Hult, P. Berglund. (2003). “Engineered enzymes for improved organic synthesis.” ScienceDirect . (online article). http://www.sciencedirect.com/science/article/pii/S095816690
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[3] P. McGrath. (2015). “The ‘Real World’ of Ethical
Decision-making: Insights from Research.” Ethical Issues in the 21st Century (online book). http://site.ebrary.com/lib/pitt/reader.action?docID=10683409
J.J. Gair, M.D. Mehta. (2001). “Social, political, legal and ethical areas of inquiry in biotechnology and genetic engineering.”
ScienceDirect. (online article). http://www.sciencedirect.com/science/article/pii/S0160791X
01000124
This scholarly, peer-reviewed article discusses ethical issues with genetic engineering as it applies to foods, pharmaceuticals, and the environment. Due to the similarities between genetic and protein engineering, these ethical issues are relevant in both fields. It details the effects that engineered proteins could have on the economy, agriculture, and humans. This source will be used to present the arguments for and against the integration of protein engineering into society.

Tylar Farmer
Patrick Bohse
K. Hult, P. Berglund. (2003). “Engineered enzymes for improved organic synthesis.” ScienceDirect . (online article). http://www.sciencedirect.com/science/article/pii/S095816690
3000958
Authored in part by Professor Emeritus of the Royal
Institute of Technology Biochemist Karl Hult, this article from a professional, peer-reviewed source details directed evolution and rational design in terms of engineering. The source also provides examples that support rational design as the superior method for protein modifications. Most importantly, the article expertly articulates how rational design is becoming progressively more viable in laboratories due to improvements in simulation models.
D.L. Parnas, P.C. Clements. (1986). “A Rational Design
Process: How and Why to Fake it.” IEEE Transactions on
Software Engineering . (online article). http://www.ics.uci.edu/~taylor/classes/121/IEEE86_Parnas_
Clement.pdf
Published in 1986 in a peer-reviewed journal and authored by software pioneer David Parnas, this article provides a guide to rational design techniques and argues that the process can be used for protein design. He acknowledges that the process will be difficult, but a viable result is possible.
This article will be used to trace rational design’s lineage and contrast Pamas’ argument with modern techniques of rational design.
A. Pollack. (2011). “New Hope of a Cure for H.I.V.”
New
York Times . (online article). http://www.nytimes.com/2011/11/29/health/new-hope-of-acure-for-hiv.html?_r=0
Published by an esteemed news company, this article describes the application of protein engineering on a person with H.I.V. It details a study in which the DNA of white blood cells was altered to create a protein needed to suppress the AIDS virus. This source demonstrates how powerful an altered protein can be and will be used as an application of protein engineering to medicine.
D. Praetorius. (2011). “Gamers Solve 15-Year AIDS Problem in 3 Weeks.” The Huffington Post . (online article). http://www.huffingtonpost.com/2011/09/19/aids-proteindecoded-gamers_n_970113.html
Published by a respected news agency, this article discusses Foldit’s largest breakthrough yet: solving the folding pattern of the Mason-Pfizer Monkey Virus, which is an important component in AIDS. The article provides little information about the actual virus, but instead focuses on how quickly Foldit’s users were able to solve the protein. The source provides user testimonies, and can be used as evidence that crowdsourcing protein solutions is practical.
“The Science behind Foldit.” (2015). Fold.it
. (website). https://fold.it/portal/info/about
Written by the developers behind Foldit, this website provides information regarding how Foldit works, the program’s importance in relation to medical research, and accolades the program has received since its release, including links to seven published research papers involving the program. This source will provide justification as to why
Foldit is an important asset to protein engineering, as well as reveal to the audience how the program functions.
“Welcome to The Fold.” (2016). Stanford University . (2016).
(website). http://folding.stanford.edu/home/
Created by the Pande Lab at Stanford University, the webpage for Folding@Home technology discusses what proteins are, why they fold, diseases caused by incorrect folding, what has been done so far, hopes for the future, and how the program works. It additionally presents a plethora of peer reviewed articles describing the applications and challenges of Folding@Home. This information will be useful in explaining Folding@Home and how it differs from
Foldit.
S. Wolpert. (2008). “Chemists Create ‘Designer Enzymes’.”
MNT . (online article). http://www.medicalnewstoday.com/releases/101236.php
Published by a site that complies with the HON code for trustworthy health information, this article details the research done by chemists from UCLA and the University of
Washington, which led to the creation of enzymes that can potentially defend against biological warfare and create more effective medications. This source exemplifies an application of protein modification to areas other than medicine.
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