April is Citizen Science Month. Citizen science — i.e., the participation of non-scientists in collaborative scientific research — can have significant impacts on societal problems, including finding a treatment for COVID-19.
Coronaviruses have a spike protein on their surface that binds tightly to a receptor protein on the surface of human cells. Once the spike binds to the receptor, the virus can infect the cell and replicate. Researchers have determined the structure of the 2019 coronavirus spike protein and how it binds to human receptors. If a protein that binds to this spike protein could be designed, it could be used to block the interaction between the spike protein and human cells — and thereby stop the infection.
Designing a protein requires an understanding of protein folding. Proteins are long chains of amino acids, and each protein folds into the lowest-energy, most-stable state it can adopt. Because there are so many degrees of freedom, the number of ways a protein can fold is astronomical. Identifying the best structure requires significant time and computing power. Two citizen science efforts are attacking this protein-folding challenge.
FoldIt is an online crowdsourcing computer game developed at the Univ. of Washington (UW) Center for Game Science and Dept. of Biochemistry. Its objective is to fold the structures of proteins as perfectly as possible. Researchers analyze the highest-scoring solutions (the lowest-energy structures) to determine whether they could be applied to solve real-world problems, such as treating diseases. Since FoldIt’s debut in 2008, gamers have had several notable successes, including deciphering the crystal structure of a retroviral protease from a monkey virus that causes HIV/AIDS-like symptoms and redesigning an enzyme that catalyzes Diels-Alder reactions to make it 18 times more potent.
In late February, FoldIt posted a puzzle that challenged players to design a binder against the 2019-nCoV coronavirus spike protein. As I write this, Round 1 of the puzzle has just closed and scientists at the UW Institute for Protein Design are reviewing the solutions submitted so far. They will first perform computational analyses to assess whether the designed proteins will fold correctly and whether they might be able to bind to the coronavirus target. Promising solutions will then advance to laboratory testing to evaluate whether they stick to the coronavirus spike protein. (A “new and improved Round 2” puzzle allows participants to continue their work and new gamers to start playing.)
Other citizen scientists are participating through the Folding@home (FAH) distributed-computing project. Individuals download the Folding@Home client, which connects their PC or Mac to a network of computers. This allows them to, in effect, donate their unused computational resources to researchers working to model the structure of the 2019-nCoV spike protein and identify sites that can be targeted by a therapeutic antibody. The data generated across many computers will be quickly and openly disseminated as part of an open science collaboration of multiple laboratories around the world.
If protein folding does not interest you, check out the many citizen science opportunities available through SciStarter (https://scistarter.org/finder) or the federal government (www.citizenscience.gov/catalog/#). With April 22 being Earth Day, you might also be interested in Earth Challenge 2020 (https://earthchallenge2020.earthday.org).
Cynthia F. Mascone, Editor-in-Chief
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