Crystal structure of a monomeric retroviral protease solved by protein folding game players

Abstract

Following the failure of a wide range of attempts to solve the crystal structure of M-PMV retroviral protease by molecular replacement, we challenged players of the protein folding game Foldit to produce accurate models of the protein. Remarkably, Foldit players were able to generate models of sufficient quality for successful molecular replacement and subsequent structure determination. The refined structure provides new insights for the design of antiretroviral drugs.

Defining the Disulfide Bonds of Insulin-like Growth Factor-binding Protein-5 by Tandem Mass Spectrometry with Electron Transfer Dissociation and Collision-induced Dissociation

“…Our results represent an extension of recent observations employing tandem MS to identify disulfide linkages in an immunoglobulin light chain (40), in human growth hormone (40), and in tissue plasminogen activator (39), three proteins in which the disulfide map had been known previously. Similar combinatorial approaches that also take advantage of the rapidly improving computational landscape of molecular modeling (51,52) should be applicable to other proteins in which the number or pattern of disulfide bonds is unknown.…”

Crowd-powered positive psychological interventions

“…For example, crowdsourcing systems have helped digitize millions of documents (Ahn, Maurer, McMillen, Abraham, & Blum, 2008), label millions of images (von Ahn & Dabbish, 2004), and classify immense planetary data (Kanefsky, Barlow, Gulick, & Norvig, 2001). In just three weeks, crowdworkers discovered the protein structure of M-PMV -a challenge that had previously eluded scientists for over ten years (Khatib et al, 2011).…”

Browser-based Harnessing of Voluntary Computational Power

“…"FoldIt players" are credited as coauthors or at least two scientific papers [42] [43]. For example, within ten days players were able to find a workable 3D structure of Mason-Pfizer monkey virus M-PMV retroviral protease -a problem for which there was no solution for previous 15 years.…”

“…FoldIt was descendant of Rosetta@Home -the participants in that project were often frustrated that they were seeing an obvious solution, but were not able to refine the results found by algorithms [43]. In FoldIt players manipulate protein structures using interactive visual tools.…”