UT Southwestern Medical Center researchers have announced that they have discovered a set of simple “rules” that nature appears to use to design proteins by examining how proteins have evolved.
Scientists have now employed these rules to create artificial proteins that look and function just like their natural counterparts.
In two papers appearing in the Sept. 22 issue of the journal Nature, Dr. Rama Ranganathan, associate professor of pharmacology, and his colleagues detail a method for creating artificial proteins based only on information they derived from analyzing certain characteristics that individual natural proteins have in common with each other.
“The goal of our research was not to find another way to make artificial proteins in the lab, but to discover the rules that nature and evolution have used to design proteins,” Dr. Ranganathan said.
“The rules we have extracted from the evolutionary record of proteins contain a substantial fraction of the information required to rebuild modern-day proteins.”
“We’re building solutions so close that, at least in a test tube, we can’t tell them apart from natural proteins.”
Dr. Ranganathan said there could still be many small differences between the artificial proteins and the natural ones, and further testing would need to be done to determine whether they work within an actual organism.
“Our work suggests that modern-day proteins have likely inherited much of the information specifying their structure and basic aspects of function from their ancestors, but it is also possible that they have been fine-tuned over time to have their own idiosyncratic features in specific cells,” said Dr. Ranganathan, who also is a Howard Hughes Medical Institute (HHMI) investigator.
“We are suggesting that the functions proteins have today are the result of fine-tuning a basic ancestral template that we have now figured out.”
“How did nature devise the right sequences that resulted in functioning proteins? Somehow, it found a way,” Dr. Ranganathan said.
“One implication of our work is that the evolutionary protein-design process may not be as complex as was previously thought.”
Earlier research has shown that for a given group of related proteins, or protein family, all family members share common structures and functions.
By examining 100 members of one protein family, the UT Southwestern group found that the proteins share a specific pattern of amino acid selection rules that are unique to that family.
“What we have found is the body of information that is fundamentally ancient within each protein family, and that information is enough to specify the structure of modern-day proteins,” Dr. Ranganathan said.
He and his team tested their discovered “rules” gleaned from the evolutionary record by feeding them into a computer program they developed.
The program generated sequences of amino acids, which the researchers then “back-translated” to create artificial genes.
Once inserted into laboratory bacteria, the genes produced artificial proteins as predicted.
“We found that when isolated, our artificial proteins exhibit the same range of structure and function that is exhibited by the starting set of natural proteins,” Dr. Ranganathan said.
“The real test will be to put them back into a living organism such as yeast or fruit flies and see how they compete with natural proteins in an evolutionary sense.”