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Gradual development of protein-like global structures through functional selection

Nature Structural Biology volume 6, pages 743–746 (1999)Cite this article

Abstract

This work focuses on streamlining the exploration of all possible sequences in an attempt to find polypeptides capable of folding into unique structures. Using a computer simulation, we have demonstrated the efficacy of constraining an 'active site' toward the correct configuration, in this case a particular conformation of a four-residue sequence, to bring about protein-like structure from a significant fraction of random sequences. The successive selections for a correct local configuration lead also to the gradual development of overall folding ability, helicity and compactness within 200 generations. The selection thus imposed alleviates an exhaustive search in sequence space.

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Figure 1: Development of protein-like structure through successive functional selections.
Figure 2: Gradual development of protein-like characteristics through functional selection.

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Acknowledgements

The authors thank P.G. Wolynes of the University of Illinois for critical comments and E.P. Ko-Mitamura for innovative discussions and suggestions in the preparation of the manuscript. This work was supported by the Japan Science and Technology Corporation and by grants from the Ministry of Education, Science, Sports and Culture, Japan.

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Authors and Affiliations

  1. Department of Biotechnology, Graduate School of Engineering, Osaka University, Osaka, 565-0871, Japan

    Tetsuya Yomo

  2. Form and Function Project, PRESTO, JST, Osaka , 565-0871, Japan

    Tetsuya Yomo

  3. Graduate School of Human Informatics, Nagoya University , Nagoya, 464-8601, Japan

    Seiji Saito & Masaki Sasai

Authors
  1. Tetsuya Yomo
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  2. Seiji Saito
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  3. Masaki Sasai
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Correspondence to Tetsuya Yomo or Masaki Sasai.

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Yomo, T., Saito, S. & Sasai, M. Gradual development of protein-like global structures through functional selection. Nat Struct Mol Biol 6, 743–746 (1999). https://doi.org/10.1038/11512

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