The AIDS epidemic especially has spurred researchers to look for a replacement for donated blood, with a potential worldwide market estimated at $10 billion. "Having a reliable, safe blood substitute is very important medically," says Carnegie Mellon University biologist Chien Ho "People are reluctant to use blood, but in surgery, trauma, and to treat many conditions you need it."
For more than 20 years, Ho and his coworkers have studied hemoglobin, the unique blood protein that carries oxygen from the lungs to the rest of the body. Ho's research aims at understanding how the structure of hemoglobin and other proteins relates to their biological function. In recent years, he has overcome several obstacles standing in the way of a hemoglobin-based blood substitute, and his current work continues in this direction, with supercomputing on the CRAY C90 playing a major role. In collaboration with Marcela Madrid of the Pittsburgh Supercomputing Center, Ho and his colleagues are using computer simulations to guide what is, in effect, a molecular renovation project -- to bioengineer hemoglobin so it does a better job delivering oxygen.
Normal and Computer-Designed Hemoglobin
In this ribbon model of hemoglobin (left), each of the four subunits is shown in a different color; the four heme groups are red.
The image on the right shows the interface region of computer-designed hemoglobin. Two subunits (blue and light blue) are shown with their associated hemes (red). In this abnormal hemoglobin, the amino acid at the beta-99 site, normally aspartic acid, is mutated to asparagine (yellow), which eliminates hydrogen bonds between the subunits, resulting in lowered cooperativity and high oxygen affinity. Changing one other amino acid -- tyrosine, alpha-42 to aspartic acid (green) -- creates new hydrogen bonds (dashed lines) with asparagine and arginine, beta-40 (gray), which partially restores cooperativity and oxygen affinity.
Researchers: Chien Ho, Carnegie Mellon University; Marcela Madrid, Pittsburgh Supercomputing Center
Hardware: CRAY Y-MP C90
Keywords: proteins, hemoglobin, blood, molecular dynamics, macromolecules, biomolecules, amino acids, cooperativity, Nuclear Magnetic Resonance (NMR), oxygen affinity, mutants, mutation, site-specific mutagenesis, AIDS.
Related Material on the Web:
Projects in Scientific Computing, PSC's annual research report.
References, Acknowledgements & Credits