Stylus: um sistema para experimentação evolucionária

sexta-feira, agosto 20, 2010

Stylus: A System for Evolutionary Experimentation Based on a Protein/Proteome Model with Non-Arbitrary Functional Constraints

Douglas D. Axe*, Brendan W. Dixon, Philip Lu

Biologic Institute, Redmond, Washington, United States of America

Abstract Top

The study of protein evolution is complicated by the vast size of protein sequence space, the huge number of possible protein folds, and the extraordinary complexity of the causal relationships between protein sequence, structure, and function. Much simpler model constructs may therefore provide an attractive complement to experimental studies in this area. Lattice models, which have long been useful in studies of protein folding, have found increasing use here. However, while these models incorporate actual sequences and structures (albeit non-biological ones), they incorporate no actual functions—relying instead on largely arbitrary structural criteria as a proxy for function. In view of the central importance of function to evolution, and the impossibility of incorporating real functional constraints without real function, it is important that protein-like models be developed around real structure–function relationships. Here we describe such a model and introduce open-source software that implements it. The model is based on the structure–function relationship in written language, where structures are two-dimensional ink paths and functions are the meanings that result when these paths form legible characters. To capture something like the hierarchical complexity of protein structure, we use the traditional characters of Chinese origin. Twenty coplanar vectors, encoded by base triplets, act like amino acids in building the character forms. This vector-world model captures many aspects of real proteins, including life-size sequences, a life-size structural repertoire, a realistic genetic code, secondary, tertiary, and quaternary structure, structural domains and motifs, operon-like genetic structures, and layered functional complexity up to a level resembling bacterial genomes and proteomes. Stylus is a full-featured implementation of the vector world for Unix systems. To demonstrate the utility of Stylus, we generated a sample set of homologous vector proteins by evolving successive lines from a single starting gene. These homologues show sequence and structure divergence resembling those of natural homologues in many respects, suggesting that the system may be sufficiently life-like for informative comparison to biology.

Citation: Axe DD, Dixon BW, Lu P (2008) Stylus: A System for Evolutionary Experimentation Based on a Protein/Proteome Model with Non-Arbitrary Functional Constraints. PLoS ONE 3(6): e2246. doi:10.1371/journal.pone.0002246

Editor: Konrad Scheffler, University of Cape Town, South Africa

Received: January 9, 2008; Accepted: April 15, 2008; Published: June 4, 2008

Copyright: © 2008 Axe et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: The work was paid for by general research funds of Biologic Institute.

Competing interests: The authors have declared that no competing interests exist.

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