Folding@home - Biomedical Research

Biomedical Research

Protein misfolding can result in a variety of diseases including Alzheimer's disease, cancer, Creutzfeldt–Jakob disease, cystic fibrosis, Huntington's disease, sickle-cell anemia, and type II diabetes. Cellular infection by viruses such as HIV and influenza also involve folding events on cell membranes. Once protein misfolding is better understood, therapies can be developed that augment cells' natural ability to regulate protein folding. Such therapies include the use of engineered molecules to alter the production of a certain protein, help destroy a misfolded protein, or assist in the folding process. The combination of computational molecular modeling and experimental analysis has the possibility of fundamentally shaping the future of molecular medicine and the rational design of therapeutics, such as expediting and lowering the costs of drug discovery. The goal of the first five years of Folding@home was to make advances in understanding folding, while the current goal is to understand misfolding and related disease, especially Alzheimer's disease.

The simulations run on Folding@home are used in conjunction with laboratory experiments, but researchers can use them to study how folding in vitro differs from folding in native cellular environments. This is advantageous in studying aspects of folding, misfolding, and their relationships to disease that are difficult to observe experimentally. For example, in 2011 Folding@home simulated protein folding inside a ribosomal exit tunnel, to help scientists better understand how natural confinement and crowding might influence the folding process. Furthermore, scientists typically employ chemical denaturants to unfold proteins from their stable native state. It is not generally known how the denaturant affects the protein's refolding, and it is difficult to experimentally determine if these denatured states contain residual structures which may influence folding behavior. In 2010, Folding@home used GPUs to simulate the unfolded states of Protein L, and predicted its collapse rate in strong agreement with experimental results.

The Pande lab is part of Stanford University, a non-profit entity, and does not sell the results generated by Folding@home. The large data sets from the project are freely available for other researchers to use upon request and some can be accessed from the Folding@home website. The Pande lab has collaborated with other molecular dynamics systems such as the Blue Gene supercomputer, and they share Folding@home's key software with other researchers, so that the algorithms which benefited Folding@home may aid other scientific areas. In 2011 they released the open-source Copernicus software, which is based on Folding@home's MSM and other parallelization techniques and aims to improve the efficiency and scaling of molecular simulations on large computer clusters or supercomputers. Summaries of all scientific findings from Folding@home are posted on the Folding@home website after publication.