This figure comes from an article about predicting protein structures with a multiplayer online ame and is titled, “Puzzles in which human predictors significantly outperformed the Rosetta ebuild and refine protocol". It is given the following description:

Human Anatomy & Physiology (11th Edition)
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ISBN:9780134580999
Author:Elaine N. Marieb, Katja N. Hoehn
Publisher:Elaine N. Marieb, Katja N. Hoehn
Chapter1: The Human Body: An Orientation
Section: Chapter Questions
Problem 1RQ: The correct sequence of levels forming the structural hierarchy is A. (a) organ, organ system,...
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In addition to in the information given in the pictures, researchers provide further descriptions for the figure stating: Players were also able to restructure b-sheets to improve hydrophobic burial and hydrogen bond quality. Automated methods have difficulty performing major protein restructuring operations to change b-sheet hydrogen-bond patterns, especially once the solution has settled in a local low-energy basin. Players were able to carry out these restructuring operations in such scenarios as strand swapping (Fig. 3) and register shifting. In one strand-swap puzzle, Foldit players were able to get within 1.1 A° of the native structure, with the top-scoring Foldit prediction being 1.4 A° away. A superposition between the starting Foldit puzzle, the top-scoring Foldit solution, and model 1 of the native NMR structure 2kpo (Protein Data Bank) are shown in Fig. 3b. Rosetta's rebuild and refine protocol, however, was unable to get within 2 A ° of the native structure (Fig. 3a, yellow points). This example highlights a key difference between humans and computers. As shown in Fig. 3c, solving the strand-swap problem required substantially unraveling the structure (Fig. 3c, bottom), with a corresponding unfavorable increase in energy (Fig. 3c, top). Players persisted with this reconfiguration despite the energy increase because they correctly recognized that the swap could ultimately lead to lower energies. In contrast, although the Rosetta rebuild and refine protocol did sample some partially swapped conformations (Fig. 3a, leftmost yellow point), these were not retained in subsequent generations owing to their relatively high energies, resulting in the top-scoring Rosetta prediction being further from the native than the starting structure. Human players are also able to distinguish which starting point will be most useful to them. Figure 3d, e shows a case where players were given ten different Rosetta predictions to choose from. Players were able to identify the model closest to the native structure, and to improve it further. Given the same ten starting models, the Rosetta rebuild and refine protocol was unable to get as close to the native structure as the top-scoring Foldit predictions. 1. Based on these descriptions, describe the trends and patterns shown in the figure. (10 sentences minimum) and explain how those trends are relevant to predicted experimental outcomes. (4 sentences minimum)
Cas
!
Rosetta energy
Transcribed Image Text:Cas ! Rosetta energy
This figure comes from an article about predicting protein structures with a multiplayer online
game and is titled, “Puzzles in which human predictors significantly outperformed the Rosetta
rebuild and refine protocol". It is given the following description:
a. Comparison of Foldit player solutions (green) to the low-energy structures sampled in
Rosetta rebuild and refine trajectories (yellow) for blind Foldit puzzle 986875 based on
the recently determined structure of 2kpo. The x axis is the all-atom r.m.s.d. to 2kpo,
and the y axis is the Rosetta energy. The starting Foldit puzzle was 4.3 AⓇ away from
the native structure (shown by the black dot on the plot); Foldit players sampled many
different conformations, with the top-scoring submission (the lowest scoring Rosetta
energy) 1.4 A away from the native structure, whereas the automated Rosetta protocol
did not sample below 2 A°. The blue dots and lines correspond to the trajectory of a
single Foldit player in c.
b. Superposition of the top scoring Foldit prediction in green with the experimentally
determined NMR model 1 in blue. The starting puzzle is in red, where the terminal
strand is incorrectly swapped with its neighbour; 8% of all Foldit players were able to
swap these strands correctly (Supplementary Table 2).
c. A score trajectory with selected structures for the top-scoring player in puzzle 986875
over a 2-h window, showing how the player explores through high-energy conformations
to reach the native state. The y axis shows the Rosetta energy and the x axis the
elapsed time in hours. The starting structure had a Rosetta energy of 2243. Each point
in the plot represents a solution produced by this player. The first structure (1) is near
the starting puzzle structure, shown as the black dot in panel a. The following structures
(2-6) are shown as blue dots in panel a. In structures 2-4, the player must explore
higher energies to move the strand into place, shown by the blue lines. In structures 5
and 6, the player refines the strand pairing.
d. Comparison of Foldit player solutions (green) to the low-energy structures sampled in
Rosetta rebuild and refine trajectories (yellow) for blind Foldit puzzle 986698 based on
the recently determined structure of 2kky. Foldit players were able to get the best Foldit
score by correctly picking from multiple alternative starting Rosetta models (black) the
model that was closest to the native structure.
e. The native structure is shown in blue with the top scoring Foldit prediction shown in
green. The top-scoring Rosetta rebuilds and refine prediction given the same ten
starting models (shown in yellow) was unable to sample as close to the native structure
as the Foldit players.
Transcribed Image Text:This figure comes from an article about predicting protein structures with a multiplayer online game and is titled, “Puzzles in which human predictors significantly outperformed the Rosetta rebuild and refine protocol". It is given the following description: a. Comparison of Foldit player solutions (green) to the low-energy structures sampled in Rosetta rebuild and refine trajectories (yellow) for blind Foldit puzzle 986875 based on the recently determined structure of 2kpo. The x axis is the all-atom r.m.s.d. to 2kpo, and the y axis is the Rosetta energy. The starting Foldit puzzle was 4.3 AⓇ away from the native structure (shown by the black dot on the plot); Foldit players sampled many different conformations, with the top-scoring submission (the lowest scoring Rosetta energy) 1.4 A away from the native structure, whereas the automated Rosetta protocol did not sample below 2 A°. The blue dots and lines correspond to the trajectory of a single Foldit player in c. b. Superposition of the top scoring Foldit prediction in green with the experimentally determined NMR model 1 in blue. The starting puzzle is in red, where the terminal strand is incorrectly swapped with its neighbour; 8% of all Foldit players were able to swap these strands correctly (Supplementary Table 2). c. A score trajectory with selected structures for the top-scoring player in puzzle 986875 over a 2-h window, showing how the player explores through high-energy conformations to reach the native state. The y axis shows the Rosetta energy and the x axis the elapsed time in hours. The starting structure had a Rosetta energy of 2243. Each point in the plot represents a solution produced by this player. The first structure (1) is near the starting puzzle structure, shown as the black dot in panel a. The following structures (2-6) are shown as blue dots in panel a. In structures 2-4, the player must explore higher energies to move the strand into place, shown by the blue lines. In structures 5 and 6, the player refines the strand pairing. d. Comparison of Foldit player solutions (green) to the low-energy structures sampled in Rosetta rebuild and refine trajectories (yellow) for blind Foldit puzzle 986698 based on the recently determined structure of 2kky. Foldit players were able to get the best Foldit score by correctly picking from multiple alternative starting Rosetta models (black) the model that was closest to the native structure. e. The native structure is shown in blue with the top scoring Foldit prediction shown in green. The top-scoring Rosetta rebuilds and refine prediction given the same ten starting models (shown in yellow) was unable to sample as close to the native structure as the Foldit players.
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