Foldit Standalone: a video game-derived protein structure manipulation interface using Rosetta

Abstract

SummaryFoldit Standalone is an interactive graphical interface to the Rosetta molecular modeling package. In contrast to most command-line or batch interactions with Rosetta, Foldit Standalone is designed to allow easy, real-time, direct manipulation of protein structures, while also giving access to the extensive power of Rosetta computations. Derived from the user interface of the scientific discovery game Foldit (itself based on Rosetta), Foldit Standalone has added more advanced features and removed the competitive game elements. Foldit Standalone was built from the ground up with a custom rendering and event engine, configurable visualizations and interactions driven by Rosetta. Foldit Standalone contains, among other features: electron density and contact map visualizations, multiple sequence alignment tools for template-based modeling, rigid body transformation controls, RosettaScripts support and an embedded Lua interpreter.Availability and ImplementationFoldit Standalone is available for download at https://fold.it/standalone, under the Rosetta license, which is free for academic and non-profit users. It is implemented in cross-platform C ++ and binary executables are available for Windows, macOS and Linux.

Design to Data for mutants of β-glucosidase B from Paenibacillus polymyxa: M319C, T431I, and K337D

“…Using a previously described method,9 three single-point mutations, M319C, T431I, and K337D were selected and modeled using FoldIt. 13 The three surface mutational changes were scored by the Rosetta energy function and are given a total system energy score (TSE).14 No mutants were selected if the changes between the wild type and variant score is predicted to be greater than +5 to enrich for proteins likelihood to fold and function.…”

RosettaAntibodyDesign (RAbD): A General Framework for Computational Antibody Design

“…Mutational analysis was done to delineate hotspot residues at the antibody-antigen interface. Rosetta was used to guide this manual analysis through the use of the PyRosetta Toolkit [86] and FoldIt Standalone [87] GUIs. Residue 7 (Lys) of the L1-11 loop of the L14_7 design was selected for mutation due to its proximity to the antigen (making hydrogen bonds to the antigen in the design model - Figure 8D) and favorable Rosetta energy.…”

Creating custom Foldit puzzles for teaching biochemistry

“…Here we introduce a new feature of Foldit called “custom contests,” in which individuals can create their own Foldit puzzle and provide it to a specific group of people, such as a class. This development builds on previous features of Foldit including “template contests,” which allow users to administer their own puzzles, selecting from a small list of predefined simple examples, and Foldit Standalone , an application version of Foldit that allows users to load in their own structures but not run them as puzzles. Custom contests can be used to create folding or design puzzles containing a wide variety of molecules, including protein, RNA, DNA, and ligands including carbohydrates, enzyme substrates, and cofactors.…”