---
title: "Rosetta@home"
chunk: 3/6
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"
---

== Disease-related research ==
In addition to basic research in predicting protein structure, docking and design, Rosetta@home is also used in immediate disease-related research.  Numerous minor research projects are described in David Baker's Rosetta@home journal. As of February 2014, information on recent publications and a short description of the work are being updated on the forum. The forum thread is no longer used since 2016, and news on the research can be found on the general news section of the project.

=== Alzheimer's disease ===
A component of the Rosetta software suite, RosettaDesign, was used to accurately predict which regions of amyloidogenic proteins were most likely to make amyloid-like fibrils. By taking hexapeptides (six amino acid-long fragments) of a protein of interest and selecting the lowest energy match to a structure similar to that of a known fibril forming hexapeptide, RosettaDesign was able to identify peptides twice as likely to form fibrils as are random proteins. Rosetta@home was used in the same study to predict structures for amyloid beta, a fibril-forming protein that has been postulated to cause Alzheimer's disease.  Preliminary but as yet unpublished results have been produced on Rosetta-designed proteins that may prevent fibrils from forming, although it is unknown whether it can prevent the disease.

=== Anthrax ===
Another component of Rosetta, RosettaDock, was used in conjunction with experimental methods to model interactions between three proteins—lethal factor (LF), edema factor (EF) and protective antigen (PA)—that make up anthrax toxin.  The computer model accurately predicted docking between LF and PA, helping to establish which domains of the respective proteins are involved in the LF–PA complex.  This insight was eventually used in research resulting in improved anthrax vaccines.

=== Herpes simplex virus 1 ===
RosettaDock was used to model docking between an antibody (immunoglobulin G) and a surface protein expressed by the cold sore virus, herpes simplex virus 1 (HSV-1) which serves to degrade the antiviral antibody.  The protein complex predicted by RosettaDock closely agreed with the especially difficult-to-obtain experimental models, leading researchers to conclude that the docking method has potential to address some of the problems that X-ray crystallography has with modelling protein–protein interfaces.

=== HIV ===
As part of research funded by a $19.4 million grant by the Bill & Melinda Gates Foundation, Rosetta@home has been used in designing multiple possible vaccines for human immunodeficiency virus (HIV).

=== Malaria ===
In research involved with the Grand Challenges in Global Health initiative, Rosetta has been used to computationally design novel homing endonuclease proteins, which could eradicate Anopheles gambiae or otherwise render the mosquito unable to transmit malaria. Being able to model and alter protein–DNA interactions specifically, like those of homing endonucleases, gives computational protein design methods like Rosetta an important role in gene therapy (which includes possible cancer treatments).

=== COVID-19 ===
In 2020, the Rosetta molecular modelling suite was used to accurately predict the atomic-scale structure of the SARS-CoV-2 spike protein weeks before it could be measured in the lab. On June 26 of 2020, the project announced it had succeeded in creating antiviral proteins that neutralize SARS-CoV-2 virions in the lab and that these experimental antiviral drugs are being optimized for animal testing trials.
In a follow-up, a paper describing 10 SARS-CoV-2 miniprotein inhibitors was published in Science on September 9. Two of these inhibitors, LCB1 and LCB3, are several times more potent than the best monoclonal antibodies being developed against SARS-CoV-2, both on a molar and mass basis. In addition, the research suggests that these inhibitors retain their activity at elevated temperatures, are 20-fold smaller than an antibody and thus, have 20-fold more potential neutralizing sites, increasing the potential efficacy of a locally administered drug. The small size and high stability of the inhibitors is expected to make them adequate to a gel formulation that can be nasally applied or as a powder to be administered directly onto the respiratory system. The researchers will work on developing these inhibitors into therapeutics and prophylactics in the months ahead. As of July 2021, these antiviral candidates were forecasted to begin clinical trials in early 2022 and had received funding from the Bill & Melinda Gates Foundation for preclinical and early clinical trials. In animal testing trials, these antiviral candidates were effective against variants of concern including Alpha, Beta and Gamma.
Rosetta@home was used to help screen the over 2 million SARS-CoV-2 Spike-binding proteins that were computationally designed, and thus, contributed to this research.
Per the Rosetta@home team at the Institute of Protein Design, Rosetta@home volunteers contributed to the development of antiviral drug candidates and to a protein nanoparticle vaccine. The IVX-411 vaccine is already on a Phase 1 clinical trial run by Icosavax while the same vaccine, licensed to another manufacturer and under the name GBP510, has been approved in South Korea for a Phase III trial run by SK Bioscience. The candidate antivirals are also going towards Phase 1 clinical trials.

=== Cancer ===
Rosetta@home researchers have designed an IL-2 receptor agonist called Neoleukin-2/15 that does not interact with the alpha subunit of the receptor. Such immunity signal molecules are useful in cancer treatment. While the natural IL-2 suffers from toxicity due to an interaction with the alpha subunit, the designed protein is much safer, at least in animal models. Rosetta@home contributed in "forward folding experiments" which helped validate designs.
In a September 2020 feature in the New Yorker, David Baker stated that Neoleukin-2/15 would begin human clinical trials "later this year". Neoleukin-2/15 is being developed by Neoleukin, a spin-off company from the Baker lab. In December 2020, Neoleukin announced it would be submitting an Investigational New Drug application with the Food and Drug Administration in order to begin a Phase 1 clinical trial of NL-201, which is a further development of Neoleukin-2/15. A similar application was submitted in Australia and Neoleukin hopes to enrol up 120 participants on the Phase 1 clinical trial. The Phase 1 human clinical trial began on May 5, 2021.