The Influence of Modularity, Seeding, and Product Inhibition on Peptide Autocatalytic Network Dynamics

Abstract

Chemical networks often exhibit emergent, systems-level properties that cannot be simply derived from the linear sum of the individual components. The design and analysis of increasingly complex chemical networks thus constitute a major area of research in Systems Chemistry. In particular, much research is focused on the emergence of functional properties in prebiotic chemical networks relevant to the origin and early evolution of life. Here, we apply a formal framework known as RAF theory to study the dynamics of a complex network of mutually catalytic peptides. We investigate in detail the influence of network modularity, initial template seeding, and product inhibition on the network dynamics. We show that these results can be useful for designing new experiments, and further argue how they are relevant to origin of life studies.

Autocatalytic Networks at the Basis of Life’s Origin and Organization

“…The earliest examples consisted simply of a system of two mutually catalytic nucleotide sequences, but later examples involved a set of nine peptides that mutually catalyze each other’s formation from shorter peptide fragments in various ways [22], or up to 16 ribozymes (catalytic RNA molecules) in a network of mutual catalysis [23]. Moreover, several of these experimental examples have been studied in more detail using the formal RAF framework, providing additional insights, and bringing theory and experiments closer together [52,53,54].…”

“…Since the formal RAF framework has already been successfully applied to the existing experimental systems, providing useful additional insights [52,53,54], such theoretical and computational studies could hopefully also serve as a guide in constructing experimental autocatalytic sets with both RNA and peptides. Furthermore, simulation studies of “partitioned” autocatalytic sets within protocells, following recent initial dynamical studies of autocatalytic sets in compartments [42], could provide additional insights into the possible early evolution of such two-polymer type systems.…”

Molecular Diversity Required for the Formation of Autocatalytic Sets

“…It is therefore useful to have a solid mathematical foundation that can be used to study the properties and dynamics of autocatalytic sets of arbitrary sizes. Such a mathematical foundation has been developed in the form of reflexively autocatalytic and food-generated (RAF; see below for a more detailed explanation) theory [12], which has also been applied successfully to study some of the existing experimental examples [13,14,15].…”

Programming Multistationarity in Chemical Replication Networks

“…[15][16][17] Recent advances in Systems Chemistry have generated new platforms for studying simple networks operating far from equilibrium, [18][19][20][21][22][23][24][25] including cooperative and competing cyclic network models such as hypercycles and autocatalytic sets. [26][27][28] In this area, we have recently studied a small peptide-based network, driven by reversible self-replication processes, [29][30][31] that exhibits bistability (Figure 1a,b). [7,24,32,33] Our experiments and extensive simulation have highlighted various mechanistic and environmental controls crucial for producing bistability, rather than typical monotonic replication.…”

“…Recent advances in Systems Chemistry have generated new platforms for studying simple networks operating far from equilibrium, including cooperative and competing cyclic network models such as hypercycles and autocatalytic sets . In this area, we have recently studied a small peptide‐based network, driven by reversible self‐replication processes, that exhibits bistability (Figure a,b) .…”