March 14, 2001--Scientists at the NEC Research Institute have discovered a way of creating artificial protein structures, the key building blocks in all living systems, a finding that could ultimately lead to the development of new pharmaceutical drugs.
Proteins are long chain molecules of amino acids with a backbone of covalently bonded atoms. In order to function properly, these chains are naturally ``folded'' into compact, precise structures. There are approximately 100,000 different types of protein chains found in humans, but only between 1,000 and 2,000 distinct types of protein folds in all of nature.
In an ongoing study at the Princeton, NJ-based NEC Research Institute, scientists used a computer to generate all possible backbone structures of a protein chain. Nearly 100 billion separate structures were generated, and the 5,000 most compact were identified as possible protein backbone candidates. Each candidate was then evaluated for folding properties similar to those of known, naturally occurring proteins and the most ``highly designable'' ones, those possessing thermodynamic stability and tolerance to the mutation of their amino acid sequences, were identified.
NEC's team, led by senior research scientists Dr. Chao Tang and Dr. Ned Wingreen; post-doctoral researcher Dr. Jonathan Miller; and Dr. Chen Zeng, a professor of physics at George Washington University, found that the most designable structure was a ``zinc finger'', a natural protein fold that is usually stabilized by a zinc ion. This fold is one of a few small protein structures that are used repeatedly in nature. Zinc-finger structures are estimated to constitute as much as one percent of the proteins encoded in the human genome.
To verify their findings, the scientists produced more refined versions of the model, with alternate backbone angles and placements of amino-acid side groups. Invariably, the zinc-finger emerged as one of the five most designable structures in each version.
``Our discovery that the zinc-finger is an optimal shape suggests that natural protein structures have been carefully selected by evolution,'' said Dr. Wingreen. ``Nature has settled upon special rare protein motifs that tolerate mutation and fold stably. It then uses these same structures over and over again.''
Research Institute scientists also discovered a set of highly designable protein backbones that have yet to be seen in nature. NEC researchers are currently designing sequences of amino acids to fold into these structures. The next step is to verify the new folds in a laboratory environment.
``The main practical motivation behind the design of new protein folds is that they may offer a new strategy for the creation of drugs, including antibiotics,'' said Dr. Wingreen. ``New protein folds may also have other biological functions, such as enabling the production of more powerful pesticides and herbicides''.
The researcher's findings may also make possible new approaches to inorganic chemistry and material engineering, since proteins are known to play an important role in the inorganic synthesis of bones, teeth and shells.
Jonathan Miller gave a presentation on the study's findings, Tuesday, March 13 at the American Physical Society Meeting in Seattle, Wash.
About NEC Research Institute
NEC Research Institute, founded in 1988 and based in Princeton, conducts basic research in the areas of computer and physical sciences. Its major research elements include Web computing; robust computing; intelligence; vision and language; devices; materials; optics; nano physics; biophysics, theoretical computer sciences and physics. For more information about the Institute, please visit its Web site at neci.nj.nec.com. |
