Computational chemistry provides insights into how the building blocks of life might have been selected

What makes the set of twenty amino acids from which almost all terrestrial life is constructed unique? It's a question chemist Henderson ("Jim") Cleaves at the Earth-Life Science Institute and colleagues have been trying to unravel.

As part of their computer modeling studies, Cleaves' team selected the parameters that define an amino acid; for example, assuming that such a molecule could only be made up of the five elements that are currently found in coded biological amino acids -- carbon, hydrogen, oxygen, nitrogen and sulfur -- and restricting possible structures to ones that would be chemically stable in a watery environment such as a cell.

Using these and other definitions, a specially designed computer program narrowed the field of amino acid candidates from tens of trillions of possibilities down to two 'virtual libraries' of alternative amino acids, one containing just over 120,000 structures and a second more restrictive one containing around 4,000¹. These results were published in the Journal of Chemical Information and Modeling.

Cleaves and colleagues also wanted to know why this particular set of twenty amino acids was so important for life. "After constructing these libraries, we wanted to see if we could compare the biological ones to random sets made from the virtual libraries, and this would tell us something about why biology uses the ones it does," says Cleaves. "Like a sort of 'movable type', with twenty amino acids, biology can make an almost infinite variety of proteins, so the question is, why those twenty 'letters'?"

When the researchers compared their virtual amino acids with the twenty amino acids coded for in biology, they found that the biological amino acids are almost perfectly tailored for the functions they need to perform. The team compared the existing set of amino acids with one billion random sets generated from their library of possible amino acids, looking at how each set represented a spread of three key properties: size, electrical charge, and hydrophobicity, or how averse a molecule is to interacting with water.

It turned out that once again, our particular set of amino acids neatly covers the ideal spread for each of these three properties². The results of this study were published in Scientific Reports.

"You can find sets that are better, but these are very rare, suggesting that if you were to find an independent example of life on another planet, it might be very similar. Even though life has a lot of chemical choices, it might end up at the same spot," Cleaves says.

The same might also be true of ribonucleic acid, or RNA -- another fundamental component of living cells, and one of two essential carriers of genetic information. As reported in Astrobiology, Cleaves and colleagues examined all of the possible permutations of RNA, and discovered that there are 227 potential stable structural arrangements, or isomers, of RNA. But once again, our particular version is highly optimized for its function³.

"RNA is both rigid and flexible, so if you want to cram two meters worth of information into a 100 micron cell, you want something that can be coiled, not something that's stiff like a rod," Cleaves says. "All of these things have highly optimal properties and there's likely a lot of evolution behind that."

ELSI chemist Jim Cleaves is studying what makes the building blocks of almost all terrestrial life on Earth unique.

References

1. Meringer, M., Cleaves II, H. J. & Freeland, S. J. Beyond terrestrial biology: Charting the chemical universe of α‑amino acid structures. Journal of Chemical Information and Modeling 53, 2851-2862 (2013).
   http://dx.doi.org/10.1021/ci400209n
2. Ilardo, M., Meringer, M., Freeland, S., Rasulev, B. & Cleaves II, H. J. Extraordinarily adaptive properties of the genetically encoded amino acids. Scientific Reports 5, 9414 (2015).
   http://dx.doi.org/10.1038/srep09414
3. Cleaves II, H. J., Meringer, M. & Goodwin, J. 227 views of RNA: Is RNA unique in its chemical isomer space? Astrobiology 15, 7 (2015).
   http://dx.doi.org/10.1089/ast.2014.1213