Predicting changes in protein thermostability brought about by single- or multi-site mutations

• Published in: BMC bioinformatics 2010-07, Vol.11 (1), p.370-370, Article 370
• Main Authors: Tian, Jian, Wu, Ningfeng, Chu, Xiaoyu, Fan, Yunliu
• Format: Article
• Language: English
• Subjects: Accuracy; Applications software; Artificial Intelligence; Classification; Gene mutations; Industrial development; Methods; Mutation; Neural networks; Programming languages; Protein engineering; Protein Stability; Proteins; Proteins - chemistry; Proteins - genetics; Software; Studies; Temperature
• ISSN: 1471-2105; 1471-2105
• DOI: 10.1186/1471-2105-11-370

An important aspect of protein design is the ability to predict changes in protein thermostability arising from single- or multi-site mutations. Protein thermostability is reflected in the change in free energy (DeltaDeltaG) of thermal denaturation. We have developed predictive software, Prethermut, based on machine learning methods, to predict the effect of single- or multi-site mutations on protein thermostability. The input vector of Prethermut is based on known structural changes and empirical measurements of changes in potential energy due to protein mutations. Using a 10-fold cross validation test on the M-dataset, consisting of 3366 mutants proteins from ProTherm, the classification accuracy of random forests and the regression accuracy of random forest regression were slightly better than support vector machines and support vector regression, whereas the overall accuracy of classification and the Pearson correlation coefficient of regression were 79.2% and 0.72, respectively. Prethermut performs better on proteins containing multi-site mutations than those with single mutations. The performance of Prethermut indicates that it is a useful tool for predicting changes in protein thermostability brought about by single- or multi-site mutations and will be valuable in the rational design of proteins.