Researchers at Howard Hughes Medical Institute (HHMI) under the lead of David Baker, a Professor of Biochemistry at the University of Washington, Seattle, have accomplished what nobody has been able to do before — the accurate prediction of the three-dimensional structure of a globular protein. They used only the amino acid sequence of this small naturally occurring protein. More than 150,000 home computers from around the world were needed to provide the computing power needed to properly process the sophisticated computational method required for this undertaking.
This accomplishment is of significant importance in the field of Molecular Biology. Being able to accurately predict a protein’s structure provides scientists with a great amount of information. Understanding the biological function of a protein can aid in the development of better and more effective structure-based drugs. Furthermore, models for crystallographic calculations can be greatly improved. The existing method of analyzing proteins, called x-ray crystallography, is time consuming and not always successful, either because the protein is not susceptible to the procedure or the level of detail is not as sufficient as needed. The new computational technique will at the very least be complementing the traditional approach of protein structure prediction, if not in the long run completely replace it.
For the last decade the team of researchers at HHMI has worked on developing more and more sophisticated computer algorithms in order to predict how a string of amino acids folds into the characteristic shape of a protein. According to the scientists this task is complicated by the fact that complex molecular side chains shape the folding process in numerous possible ways. Furthermore, proteins may get permanently trapped in a not completely folded structure. With the multitude of possible outcomes one can only imagine the magnitude of a computer program needed to accurately predict such a protein structure.
One of the main programs used by the researchers at HHMI is called Rosetta. The program essentially sorts the potential shapes of a protein. If the program identifies a potential shape or section of a shape as unstable, it marks it for what the scientists call ‘targeted rebuilding.’ Through ‘targeted rebuilding’ the unstable portion of the structure can be analyzed and rebuild until a stable version is found. The ultimate goal is to find the ‘lowest-energy structure of a folded protein,’ which the researchers have found to be the most stable and accurate prediction of a protein structure. The researchers have tested the program with amazing accuracy on known protein structures proving that their computational method works.