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Real value prediction of protein folding rate change upon point mutation

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Abstract

Prediction of protein folding rate change upon amino acid substitution is an important and challenging problem in protein folding kinetics and design. In this work, we have analyzed the relationship between amino acid properties and folding rate change upon mutation. Our analysis showed that the correlation is not significant with any of the studied properties in a dataset of 476 mutants. Further, we have classified the mutants based on their locations in different secondary structures and solvent accessibility. For each category, we have selected a specific combination of amino acid properties using genetic algorithm and developed a prediction scheme based on quadratic regression models for predicting the folding rate change upon mutation. Our results showed a 10-fold cross validation correlation of 0.72 between experimental and predicted change in protein folding rates. The correlation is 0.73, 0.65 and 0.79, respectively in strand, helix and coil segments. The method has been further tested with an extended dataset of 621 mutants and a blind dataset of 62 mutants, and we observed a good agreement with experiments. We have developed a web server for predicting the folding rate change upon mutation and it is available at http://bioinformatics.myweb.hinet.net/fora.htm.

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Acknowledgments

We thank the anonymous reviewers for their constructive comments to improve the manuscript.

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Authors and Affiliations

  1. Department of Biotechnology, Mingdao University, Changhua, 523, Taiwan

    Liang-Tsung Huang

  2. Department of Biotechnology, Indian Institute of Technology (IIT) Madras, Chennai, 600 036, Tamilnadu, India

    M. Michael Gromiha

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  1. Liang-Tsung Huang
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  2. M. Michael Gromiha
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Correspondence to M. Michael Gromiha.

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Huang, LT., Gromiha, M.M. Real value prediction of protein folding rate change upon point mutation. J Comput Aided Mol Des 26, 339–347 (2012). https://doi.org/10.1007/s10822-012-9560-3

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  • DOI: https://doi.org/10.1007/s10822-012-9560-3

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