Jeffrey Skolnick and coworkers at the Georgia Tech School of Biology have shown that the ability to catalyze biochemical reactions is an intrinsic property of protein molecules, defined only by their structure and the principles of chemistry and physics. Their study was published on Feb. 23, 2016, in the open-access journal F1000Research.

The finding suggests that where proteins exist, life is possible because biochemical transformations are possible. And because biochemical transformations are required for life, life as we know it could be ubiquitous in the universe.

Life on Earth depends on myriad biochemical reactions mediated by proteins. The conventional wisdom is that the biochemical properties of proteins arise from evolutionary selection. According to the new study, evolution is not necessary for the existence of proteins’ biochemical functions, although evolutionary selection may have optimized proteins for specific roles.

The study’s conclusion is profound, said Terry Snell, chair of the School of Biology, in the College of Sciences. That’s because “the impression of design pervades biology,” he explained. “All the exquisite structures in biology—such as the complex anatomy of the vertebrate eye or the molecular structure of enzymes—are thought to have arisen by adaptation directed by natural selection. The new paper suggests that a considerable portion of the design in biology can be attributed to physical and chemical laws that dictate the function and structure of proteins.”

Ron Elber concurs. He is the W.A. “Tex” Moncrief Chair in Computational Life Sciences and Biology at the University of Texas at Austin. The work “suggests that physical principles assist nature in selecting proteins for specific functions,” he said. “While selection is necessary, it is useful to reduce the number of possibilities, and the Skolnick study suggests a mechanism of how that might happen.”

Skolnick and coworkers Mu Gao and Hongyi Zhou at the Center for the Study of Systems Biology studied the properties of a library of artificially generated proteins selected only for their intrinsic stability, not any type of function. They found that a remarkable number of the artificial proteins have the unique features of functional proteins, including binding pockets to accommodate small molecules. These pockets are necessary for biochemical catalysis to take place.

Although Skolnick and coworkers studied only a small ensemble of protein-like molecules, Elber observed, “it nevertheless includes features that resemble active sites even though it was generated on the basis of physical principles only.”

The researchers further predicted computationally that some members of the artificial, nonfunctional protein library would have strong protein-protein and protein-DNA interactions. Such interactions are essential in the machinery of life as we know it.

“The biochemical seeds of life could be prevalent,” Skolnick said. “If you rain meteorites containing amino acids and somehow these polymerize to form small proteins, then a subset of these would fold to stable structure and a small subset of these could engage in rudimentary metabolism, all without any selection for biochemical function. Thus, the background probability for function is much larger than had been previously appreciated.”

In a manuscript in preparation, Skolnick and coworkers have built on this finding to propose a mechanism for the emergence of chirality in biology. Many compounds can have the same structure and physical properties but differ only in their right- or left-handed orientation. In the presence of other biological molecules, such as proteins, usually only the compounds with one type of handedness—or chirality—can react. In nature, one type of handedness prevails. And how this prevalence emerged has been the subject of years of research.