---
title: "Rosetta@home"
chunk: 5/6
source: "https://en.wikipedia.org/wiki/Rosetta@home"
category: "reference"
tags: "science, encyclopedia"
date_saved: "2026-05-05T03:25:41.390646+00:00"
instance: "kb-cron"
---

=== Robetta ===
The Robetta (Rosetta Beta) server is an automated protein structure prediction service offered by the Baker laboratory for non-commercial ab initio and comparative modeling.  It has participated as an automated prediction server in the biannual CASP experiments since CASP5 in 2002, performing among the best in the automated server prediction category. Robetta has since competed in CASP6 and 7, where it did better than average among both automated server and human predictor groups. It also participates in the CAMEO3D continuous evaluation. Robetta tasks run on Baker lab servers, Janelia Research Campus machines, and Rosetta@home participant computers.
In modeling protein structure as of CASP6, Robetta first searches for structural homologs using BLAST, PSI-BLAST, and 3D-Jury, then parses the target sequence into its individual domains, or independently folding units of proteins, by matching the sequence to structural families in the Pfam database.  Domains with structural homologs then follow a "template-based model" (i.e., homology modeling) protocol.  Here, the Baker laboratory's in-house alignment program, K*sync, produces a group of sequence homologs, and each of these is modeled by the Rosetta de novo method to produce a decoy (possible structure).  The final structure prediction is selected by taking the lowest energy model as determined by a low-resolution Rosetta energy function.  For domains that have no detected structural homologs, a de novo protocol is followed in which the lowest energy model from a set of generated decoys is selected as the final prediction.  These domain predictions are then connected together to investigate inter-domain, tertiary-level interactions within the protein.  Finally, side-chain contributions are modeled using a protocol for Monte Carlo conformational search.
In CASP8, Robetta was augmented to use Rosetta's high resolution all-atom refinement method, the absence of which was cited as the main cause for Robetta being less accurate than the Rosetta@home network in CASP7. In CASP11, a way to predict the protein contact map by co-evolution of residues in related proteins called GREMLIN was added, allowing for more de novo fold successes.

=== Other Rosetta servers ===
Rosetta is available as an online service from a number of other public servers. ROSIE offers a variety of functions from RNA structure prediction and design to ligand docking and antibody modeling.

=== Foldit ===

On May 9, 2008, after Rosetta@home users suggested an interactive version of the volunteer computing program, the Baker lab publicly released Foldit, an online protein structure prediction game based on the Rosetta platform.  As of September 25, 2008, Foldit had over 59,000 registered users.  The game gives users a set of controls (for example, shake, wiggle, rebuild) to manipulate the backbone and amino acid side chains of the target protein into more energetically favorable conformations.  Users can work on solutions individually as soloists or collectively as evolvers, accruing points under either category as they improve their structure predictions.
Foldit can work as a GUI frontend to Rosetta under a tailored "professional mode".

=== RoseTTAFold ===
RoseTTAFold, which is inspired by AlphaFold, uses a neural network to predict the distance and orientation between residues. These predictions guide Rosetta software in producing a structure. RoseTTAFold is open source under the MIT license.

=== Non-Baker lab branches ===
The Jianyi Yang lab in China offers a modified version of Rosetta termed tr-RosettaX2 (transform-restrained Rosetta). It uses a deep learning-based contact prediction method different from RoseTTAFold to guide the usual Rosetta folding algorithm. trRosetta predates RoseTTAFold.

== Comparison to similar volunteer computing projects ==
There are several volunteer computed projects which have study areas similar to those of Rosetta@home, but differ in their research approach:

=== Folding@home ===
Of all the major volunteer computing projects involved in protein research, Folding@home is the only one not using the BOINC platform. Both Rosetta@home and Folding@home study protein misfolding diseases such as Alzheimer's disease, but Folding@home does so much more exclusively. Folding@home almost exclusively uses all-atom molecular dynamics models to understand how and why proteins fold (or potentially misfold, and subsequently aggregate to cause diseases). In other words, Folding@home's strength is modeling the process of protein folding, while Rosetta@home's strength is computing protein design and predicting protein structure and docking.
Some of Rosetta@home's results are used as the basis for some Folding@home projects. Rosetta provides the most likely structure, but it is not definite if that is the form the molecule takes or whether or not it is viable. Folding@home can then be used to verify Rosetta@home's results, and can provide added atomic-level information, and details of how the molecule changes shape.
The two projects also differ significantly in their computing power and host diversity. Averaging about 6,650 teraFLOPS from a host base of central processing units (CPUs), graphics processing units (GPUs), and (formerly) PS3s, Folding@home has nearly 108 times more computing power than Rosetta@home.

=== World Community Grid ===
Both Phase I and Phase II of the Human Proteome Folding Project (HPF), a subproject of World Community Grid, have used the Rosetta program to make structural and functional annotations of various genomes.  Although he now uses it to create databases for biologists, Richard Bonneau, head scientist of the Human Proteome Folding Project, was active in the original development of Rosetta at David Baker's laboratory while obtaining his PhD. More information on the relationship between the HPF1, HPF2 and Rosetta@home can be found on Richard Bonneau's website.

=== Predictor@home ===
Like Rosetta@home, Predictor@home specialized in protein structure prediction. While Rosetta@home uses the Rosetta program for its structure prediction, Predictor@home used the dTASSER methodology. In 2009, Predictor@home shut down.
Other protein related volunteer computing projects on BOINC include QMC@home, Docking@home, POEM@home, SIMAP, and TANPAKU.  RALPH@home, the Rosetta@home alpha project which tests new application versions, work units, and updates before they move on to Rosetta@home, runs on BOINC also.