Prediction of Protein Thermostability by an Efficient Neural Network Approach

Introduction: Manipulation of protein stability is important for understanding the principles that govern protein thermostability, both in basic research and industrial applications. Various data mining techniques exist for prediction of thermostable proteins. Furthermore, ANN methods have attracted significant attention for prediction of thermostability, because they constitute an appropriate approach to mapping the non-linear input-output relationships and massive parallel computing.Method: An Extreme Learning Machine (ELM) was applied to estimate thermal behavior of 1289 proteins. In the proposed algorithm, the parameters of ELM were optimized using a Genetic Algorithm (GA), which tuned a set of input variables, hidden layer biases, and input weights, to and enhance the prediction performance. The method was executed on a set of amino acids, yielding a total of 613 protein features. A number of feature selection algorithms were used to build subsets of the features. A total of 1289 protein samples and 613 protein features were calculated from UniProt database to understand features contributing to the enzymes’ thermostability and find out the main features that influence this valuable characteristic.Results:At the primary structure level, Gln, Glu and polar were the features that mostly contributed to protein thermostability. At the secondary structure level, Helix_S, Coil, and charged_Coil were the most important features affecting protein thermostability. These results suggest that the thermostability of proteins is mainly associated with primary structural features of the protein. According to the results, the influence of primary structure on the thermostabilty of a protein was more important than that of the secondary structure. It is shown that prediction accuracy of ELM (mean square error) can improve dramatically using GA with error rates RMSE=0.004 and MAPE=0.1003.Conclusion: The proposed approach for forecasting problem significantly improves the accuracy of ELM in prediction of thermostable enzymes. ELM tends to require more neurons in the hidden-layer than conventional tuning-based learning algorithms. To overcome these, the proposed approach uses a GA which optimizes the structure and the parameters of the ELM. In summary, optimization of ELM with GA results in an efficient prediction method; numerical experiments proved that our approach yields excellent results.Keywords: Protein Stability, Primary and secondary structures, Extreme learning machine, Neural networks, Genetic algorithm