---
title: "Rosetta@home"
chunk: 4/6
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"
---

== Rosetta software ==
 
Rosetta is the software responsible for performing structure prediction in Rosetta@home. Besides a BOINC cluster, Rosetta can run on a single local computer, or on a local supercomputer. Similar to other bioinformatic programs, there are online public servers offering to run Rosetta from a web interface. The software is freely licensed to the academic community and available to pharmaceutical companies for a fee.
Originally introduced by the Baker laboratory at the University of Washington in 1998 as an ab initio approach to structure prediction, Rosetta has since branched into several development streams and distinct services, providing features such as macromolecular docking and protein design. Many of the graduate students and other researchers involved in Rosetta's initial development have since moved to other universities and research institutions, and subsequently enhanced different parts of the Rosetta project.
The Rosetta platform derives its name from the Rosetta Stone, as it attempts to decipher the structural "meaning" of proteins' amino acid sequences. Development of the Rosetta code is done by Rosetta Commons. Rosetta participates in  CASP and CAPRI.
Rosetta was rewritten in C++ to allow easier development than that allowed by its original version, which was written in Fortran.  This new version is object-oriented, and was released to Rosetta@Home February 8, 2008.

=== RosettaDesign ===

RosettaDesign, a computing approach to protein design based on Rosetta, began in 2000 with a study in redesigning the folding pathway of Protein G. In 2002 RosettaDesign was used to design Top7, a 93-amino acid long α/β protein that had an overall fold never before recorded in nature.  This new conformation was predicted by Rosetta to within 1.2 Å RMSD of the structure determined by X-ray crystallography, representing an unusually accurate structure prediction. Rosetta and RosettaDesign earned widespread recognition by being the first to design and accurately predict the structure of a novel protein of such length, as reflected by the 2002 paper describing the dual approach prompting two positive letters in the journal Science, and being cited by more than 240 other scientific articles. The visible product of that research, Top7, was featured as the RCSB PDB's 'Molecule of the Month' in October 2006; a superposition of the respective cores (residues 60–79) of its predicted and X-ray crystal structures are featured in the Rosetta@home logo.
Brian Kuhlman, a former postdoctoral associate in David Baker's lab and now an associate professor at the University of North Carolina, Chapel Hill, offers RosettaDesign as an online service.

=== RosettaDock ===
RosettaDock was added to the Rosetta software suite during the first CAPRI experiment in 2002 as the Baker laboratory's algorithm for protein–protein docking prediction. In that experiment, RosettaDock made a high-accuracy prediction for the docking between streptococcal pyogenic exotoxin A and a T cell-receptor β-chain, and a medium accuracy prediction for a complex between porcine α-amylase and a camelid antibody.  While the RosettaDock method only made two acceptably accurate predictions out of seven possible, this was enough to rank it seventh out of nineteen prediction methods in the first CAPRI assessment.
Development of RosettaDock diverged into two branches for subsequent CAPRI rounds as Jeffrey Gray, who laid the groundwork for RosettaDock while at the University of Washington, continued working on the method in his new position at Johns Hopkins University. Members of the Baker laboratory further developed RosettaDock in Gray's absence.  The two versions differed slightly in side-chain modeling, decoy selection and other areas. Despite these differences, both the Baker and Gray methods performed well in the second CAPRI assessment, placing fifth and seventh respectively out of 30 predictor groups. Jeffrey Gray's RosettaDock server is available as a free docking prediction service for non-commercial use.
In October 2006, RosettaDock was integrated into Rosetta@home.  The method used a fast, crude docking model phase using only the protein backbone.  This was followed by a slow full-atom refinement phase in which the orientation of the two interacting proteins relative to each other, and side-chain interactions at the protein–protein interface, were simultaneously optimized to find the lowest energy conformation.  The vastly increased computing power afforded by the Rosetta@home network, combined with revised fold-tree representations for backbone flexibility and loop modeling, made RosettaDock sixth out of 63 prediction groups in the third CAPRI assessment.