Some of the tasks EGAD can perform are: prediction of mutation effects on protein stability and protein-complex formation to within ~1kcal/mol, automated scanning mutagenesis, including saturation mutagenesis, of proteins and protein complexes, total protein sequence design, design of ligand binding sites, optimization of sequences while considering multiple structures for the design of specific binding proteins and conformational switching, predicting the pK's of ionizable groups in proteins, and generating tables to display the distribution of energetic interactions in protein structures.

"The database aims to collect all folding data into one repository and, within the framework of the International Foldeomics Consortium (http://www.foldeomics.org), encourage sharing and data analysis. We are particularly interested in allowing the graphical analysis of raw-data on the site."

You can register to do advanced searches and to submit your own protein folding data.

While it is generally understood that proper protein folding happens spontaneously, scientists are still trying to understand what causes a particular protein to fold properly or go awry. The protein’s local environment plays a role, and other molecules in the neighborhood can assist or hinder the process, says Gierasch.

“It’s a delicate balance—proteins can tip to the dark side very readily,” she says.

Recently researchers have developed techniques that allow them to follow the fate of individual proteins within cells. Using an experimental set-up that they designed to do just that, Gierasch and Ignatova decided to see how the small molecule proline influenced protein folding. Proline is often taken up by cells in response to water loss, and other molecules with similar cellular roles have been shown to inhibit improper folding.

“There have been conflicting results,” says Gierasch, “In some cases these molecules inhibit misfolding, in some cases they promote it.”

This study was presented here on June 23rd at the Annual European Congress of Rheumatology (EULAR) on behalf of the Fibrillex Amyloid Secondary Trial (FAST) Group by Bouke P.C. Hazenberg, MD, coinvestigator and consultant in rheumatology, rheumatology, and clinical immunology at the University Medical Centre Groningen in Groningen, The Netherlands.

Amyloidosis is a protein-folding disorder that can occur in diseases characterized by extracellular deposition of insoluble fibrillar proteinaceous material, thereby resulting in loss of function of the tissue or organ involved.

A series of discussions in a campus café in Lausanne has blossomed into an extraordinary collaboration between EPFL physics professor Paolo De Los Rios and University of Lausanne biology professor Pierre Goloubinoff. Using the principles of statistical physics, they have identified a simple, single mechanism that explains the mechanical role of molecular chaperones in protein folding and translocation, settling at the same time a long-standing controversy over this process.

Previously, the rise in the level of p53 in cells whose DNA had been damaged was thought to be due only to a decrease in the rate at which the p53 protein is broken down in the cell. The St. Jude study showed that the level of p53 protein synthesis increases following DNA damage. This discovery suggests that scientists can use this newly recognized mechanism to modulate p53 function in the cell in order to control whether cells in the body mutate, and whether cells live or die after DNA damage. A report on this work appears in the October 7 issue of the journal Cell.

The paper in today's Journal of Biological Chemistry by Professor of Biochemistry and Molecular Biology William Dowhan, Ph.D., and colleagues shows that phospholipids, which make up the permeable barrier of cell membranes, play a direct role in the folding of membrane proteins – proteins that penetrate the membrane or bind to either side of it.

"What we've demonstrated again is that it's not just a membrane protein's genetically determined sequence that dictates how it folds so that it can function properly. Its lipid environment also plays a role," Dowhan said. "People used to assume that specific lipids made no difference."

In the JBC paper, Dowhan and colleagues looked at how a protein called GabP, which transports an amino acid across the membrane of the bacterium E. coli, is affected by the presence of a phospholipid named phosphatidylethanolamine, or PE for short.

The array offers scientists a cutting edge research tool allowing them to analyze the specificities of glycan binding proteins (GBP's), which function through their binding to such sugar chains.