Predicting Protein Folding Hotspots And Drug Discovery

Filed in archive Drugs, Vaccines and Therapeutics , Genomics, Proteomics and Bioinformatics on December 19, 2005

A number of diseases are associated with protein aggregation and the formation and accumulation of amyloid fibers, including Parkinson's, Alzheimer's and Creuzfeldt-Jacob disease, as well as pancreatic insufficiency, which causes type 2 diabetes.

Scientists from the Universitat Aut�noma de Barcelona developed a method to identify specific "hot spots" in proteins linked to these diseases. These hot spots are the regions where the proteins are most likely to fold and aggregate into amyloid fibers. According to the authors, their findings may provide the basis for designing drugs that will prevent such protein folding, subsequently preventing the onset of the above-mentioned deiseases.

In unfolded protein chains, identifying the hotspots may useful in designing drugs that can completely cover and shield the hot spots, thus preventing these stretches from coming into contact with other proteins and aggregate. In globular proteins, drugs must be aimed at stabilising the structure of the protein, preventing the "hot spots" from becoming exposed externally.

This research is recently published in BMC Structural Biology (fully access available).

Source: UAB News
Photo Credit: BioMed Central: Representation of the 3D structure of globular proteins related to disease. The chain segments in which the prediction and the experimental data coincide are colored in green. Those identified experimentally to be relevant for amyloid formation but not predicted by the present approach are colored in blue. The regions predicted to be important for amyloid formation from which experimental data are not available or indicates that they are not involved in aggregation are shown in yellow.