Are We There Yet?

by Matt J. Carlson

In a dramatic step toward manufacturing (not quite "creating") life, a team of Caltech scientists has successfully designed and synthesized a protein "from scratch."⁽¹⁾ While this achievement certainly deserves our applause, opinion remains divided over how (and how much) it impacts the origin-of-life debate. Some interpret the success as evidence for life's capacity to self-assemble; others see it as further corroboration of the necessity for a Creator. Many relevant questions must be considered, including this one: What resources went into the design and building of the protein?

In addition to prior knowledge-intricate knowledge-of what a protein is and does, the project required an array of essential biochemical components, a controlled environment for survival of these components, and someone to recognize success when it was achieved. The project also relied crucially on the use of sophisticated computer technology.

Given that a 28-amino-acid protein (near the lower limit of protein size) was their target, researchers had to determine which of 20 natural amino acids should be placed in which of 28 positions along the amino acid chain to make a viable protein, one that would fold itself into a functional configuration. That means 20²⁸ (or 10³⁶) amino acid sequences needed trial-and-error checking. Using a mathematical tool called the dead-end elimination theorem,⁽²⁾ the computer simplified the task somewhat, just as ignoring the center pieces of a puzzle simplifies the completion of the edges. Even with this simplification, however, the program took 90 CPU hours to perform the calculation and generate a workable protein design.

Finally, the chosen sequence of amino acids was synthesized in the lab, and the protein did, indeed, fold into the desired configuration. What a triumph! And what a huge investment was required to produce something many times simpler than most proteins, including those necessary for life! (A GroEL protein molecule, for example, is comprised of 548 amino acids.) Remember that to generate the design of a protein with only twice as many amino acids (56) would take much more than double the computational time (and effort)-just as guessing a two-digit number is more than twice as difficult as guessing a single digit. Imagine trying to guess a 500+ digit number, or acid sequence.

If no "right" number-or "right" sequence-exists, any guess is as good as another. But since there is a "right" answer, one that leads to life, whose Mind established it?

References:
1. Bassil I. Dahiyat and Stephen L. Mayo, "De Novo Protein Design: Fully Automated Sequence Selection," Science, 278 (1997), pp. 82-87.
2. J. Desmet, et al, "The Dead-End Elimination Theorem and its use in Protein Side-Chain Positioning," Nature, 356 (1992), pp. 539-542.

Matt Carlson, a Caltech graduate student, will complete his Ph.D. in computational biochemistry in spring 1998. He and his wife, Erica, serve as RTB volunteer apologists and work with junior high kids at their church in Pasadena, California.