As a molecular machine found in all living cells that is of central importance for the synthesis of the proteins upon which all life depends, the ribosome is perhaps the primordial example of a molecular machine. For this reason, a recent Open Access publication in the Journal of Molecular Modeling is of substantial interest to those wishing to understand how molecular machines could evolve to execute complex functions. “An information-carrying and knowledge-producing molecular machine. A Monte-Carlo simulation” presents a computer simulation of how, by a long sequence of chemical steps, a simple self-replicating oligomer in a specific environment could evolve into a machine to translate a genetic code into amino acid sequences. [Be sure to download the supplemental material as well as the main text because the supplemental figures make it much easier to follow the author’s argument.]

The analysis begins with the postulate of a simple RNA-like oligomer that is capable of replicating itself, although in an error-prone fashion that leads to frequent mutations. It further postulates a specific environment, such as porous rock, that prevents the replicated aggregates from diffusing away through the small pores. As replication errors lead to larger aggregates, regions of the porous rock that were initially unfavorable because the pores were large enough to permit the replicated aggregates to diffuse away now become populated by the evolved aggregates that are too large to diffuse through these pores.

In further molecular evolution, strands that form hairpins are selected because the hairpin protects the strand from degradation. Several hairpins can then bind along an open strand with sequences complementary to the loops of the hairpins. In the computer simulation, aggregates are assigned fitness scores according to the number of hairpins in the aggregate. Aggregates composed of hairpins of one kind are favored because they form a more compact aggregate. In further steps, single amino acids can attach to an open end of a hairpin, and adjacent amino acids can oligomerize to form a peptide. Peptides that can agglutinate to form an envelope are favored by Darwinian selection leading to a primitive translation apparatus in which RNA molecules produce protein molecules.

The simulation reveals a plausible mechanism by which an environment that selects compact molecular aggregates isolated from their environments can lead to novel functions. Slowly molecules with “knowledge” of how to function in their specific environments evolve through the elimination of sequences that don’t work. Are there ideas here that could be useful in the design or laboratory evolution of artificial molecular machines?

Earlier papers on computer simulation of the origin of life by Christoph and Hans Kuhn, which provide more background to the ideas presented in this paper, can be downloaded here (from the web site for Hans Kuhn’s textbook Principles of Physical Chemistry).