© Animation Research Labs, University of Washington. With permission.

Because of neurologic maladies (lupus and Chiari Malformation; the combination of which

rendered an initial misdiagnosis of multiple sclerosis) with which I have been afflicted
for almost 2 decades, substantial nutritional protein intake is a major determinant
in my physiological functioning.

Portions of my RDA (recommended daily allowance) of the fun factor, though, are also derived from protein: protein-folding, that is. A collaborative team of computer scientists, biochemists, and bioengineers at the University of Washington provides that experience for me and 100K+ MMO (massively

multiplayer online) gamers, released through its 3D molecular modelling software known as Foldit.

As a former student of architecture, I translated Foldit's fundamental premise: that form follows
function. A protein's optimal, intended functioning is predicated upon primary
structuring of its inherent amino acid sequencing; a stabilized environment buttressed
by strong hydrogen bonds in which the folding process occurs; all of which predetermines
the eventual native 3D structure. Playing the game, I became acquainted with concepts
of hydrophobic collapse, steep walls, and energy landscapes, partially-folded proteins
trapped within poorly-defined structures. Flawed protein formation follows malevolent
intent inherent within faulty engineering of its amino acids. Pathology –understood
within context of the game- is a matter of molecular design failure. Foldit's
proteomic tool meets the challenge of death by design by utilizing human visualization to discover and disrupt pathways of misfolded malfunction in proteins.

© Animation Research Labs, University of Washington. With permission.
Image:Puzzle 48. Unfolded protein.

Having suffered paralysis, stroke, ischemia, seizures, and migraines, I now perceive spatially the ravaging biochemical battle within, waged against the vulnerable, predisposed proteins of my cell nuclei; and can comprehend more acutely my experience with apoptosis - "programmed cell death". Interacting with the Foldit simulations, I wonder what antagonized those assassinating antibodies
into killing my neurons? What environmental provocation has engaged and conscripted
my proteins for almost 2 decades? Might
a high-scoring Foldit gamer
discover through play the means of blocking NR2 proteins from annihilating antibodies in a lupus case such as mine? Is it possible that the spinal fluid which may have built up as a result of my Chiari Malformation provide the anti-DNA sample test for my lupus? My challenge was to game while simultaneously grasping the inverse: in ailments such as Alzheimer's disease, the active, malformed proteins themselves are the agents provocateurs. Will Foldit's predictive gaming applications ultimately be the pattern-matching breakthrough mechanism by which and through

which dysfunctional protein links along the autoimmune chain will first be broken, thereby directing biomedicine's way forward in drug-discovery and leading biotech in the freeing of disease-burdened
bodies from currently-incurable anomalies?

©Animation Research Labs, University of Washington. With permission. Image: Protein conformation in progress.

Quite possibly. Foldit gamers have garnered top-winning places for their solutions in the CASP8

(Critical Assessment of Techniques for Protein Structure Prediction) competition. Cybervolunteers
first practice on known human protein structures and advance to more difficult
conformations for which optimal folding is not yet understood.

Foldit regularly receives requests for creation of protein puzzles as supplementary homework assignments for college students. Having recently read a grant proposal abstract submitted by the research team to the MacArthur Foundation for the underwriting of a STEM gaming initiative for middle and high school students,

I had occasion to query Dr. Zoran Popović (Associate Professor in University of Washington's Department of project) about the game vis-à-vis NanoScience/NanoTechnology and its particular implications for NanoMedicine.

Thus spoke Zoran: "With recent introduction of design puzzles, and future direct connections with researchers working on drug
and vaccine design, we intend to pioneer a new research cycle, where lab
experiments are driven by the results of Foldit design challenge puzzles.
We are also looking to design new games specifically towards creation of
nano-machines. We think that people will be particularly good at
designing new nano-structures. All that is missing is a way for them to
directly experiment in the nano-physics world." (quoted with permission)

"We are developing new genre of science-centric serious games, including games that lead to scientific discoveries in biochemistry with implications towards curing diseases,
discovering vaccines, and developing novel biofuels." (quoted from
Popović 's UW bio webpage)

Among the other game development project members working in collaboration with Dr. Popović is Dr. David Baker (Professor of Biology, Adjunct Professor of Genome Sciences and Bioengineering at
University of Washington). Baker was a winner in the 2008 Sackler International Prize in Biophysics in the field of the physics of structure formation and self-assembly of proteins and nucleic acids.
Baker was awarded the Foresight Nanotech Institute Feynman Prize for Theory in 2004.

"The goals of David Baker’s research group are to develop robust methods to accurately compute the
structures of biological macromolecules and interactions, and to design and
experimentally validate novel macromolecules with new and useful functions.
Recent highlights include the computational design of novel enzymes catalyzing
reactions not catalyzed by naturally occurring enzymes, the blind prediction of
structures of small proteins with atomic level accuracy, and the enlisting of the
computers and brain power of people around the world to bear on these problems
through Rosetta@home and FoldIt." (quoted from Baker
's Faculty web page)

© Animation Research Labs, University of Washington. With permission. Image: Puzzle 48. Folded protein.

From the macro to the micro to the nano, from the known to the unknown, TINC members are encouraged to participate and compete in the CASP9 experiment

and to sign on in the name of science.

[Disclosure statement: Although this blog is hosted on a European site, I'm transmitting from USA, whose Federal Trade Commission requires that bloggers disclose financial compensations and material connections between themselves and subjects/objects of their writing. So, I now do declare that no funding has come my way as a result of this review of the Foldit game. It is featured here in keeping with the NanoGaming theme of Kanada's Kids].

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