KStable: A Computational Method for Predicting Protein Thermal Stability Changes by K-Star with Regular-mRMR Feature Selection.

Thermostability is a protein property that impacts many types of studies, including protein activity enhancement, protein structure determination, and drug development. However, most computational tools designed to predict protein thermostability require tertiary structure data as input. The few tools that are dependent only on the primary structure of a protein to predict its thermostability have one or more of the following problems: a slow execution speed, an inability to make large-scale mutation predictions, and the absence of temperature and pH as input parameters. Therefore, we developed a computational tool, named KStable, that is sequence-based, computationally rapid, and includes temperature and pH values to predict changes in the thermostability of a protein upon the introduction of a mutation at a single site. KStable was trained using basis features and minimal redundancy-maximal relevance (mRMR) features, and 58 classifiers were subsequently tested. To find the representative features, a regular-mRMR method was developed. When KStable was evaluated with an independent test set, it achieved an accuracy of 0.708.

iStable 2.0: Predicting protein thermal stability changes by integrating various characteristic modules.

Protein mutations can lead to structural changes that affect protein function and result in disease occurrence. In protein engineering, drug design or and optimization industries, mutations are often used to improve protein stability or to change protein properties while maintaining stability. To provide possible candidates for novel protein design, several computational tools for predicting protein stability changes have been developed. Although many prediction tools are available, each tool employs different algorithms and features. This can produce conflicting prediction results that make it difficult for users to decide upon the correct protein design. Therefore, this study proposes an integrated prediction tool, iStable 2.0, which integrates 11 sequence-based and structure-based prediction tools by machine learning and adds protein sequence information as features. Three coding modules are designed for the system, an Online Server Module, a Stand-alone Module and a Sequence Coding Module, to improve the prediction performance of the previous version of the system. The final integrated structure-based classification model has a higher Matthews correlation coefficient than that of the single prediction tool (0.708 vs 0.547, respectively), and the Pearson correlation coefficient of the regression model likewise improves from 0.669 to 0.714. The sequence-based model not only successfully integrates off-the-shelf predictors but also improves the Matthews correlation coefficient of the best single prediction tool by at least 0.161, which is better than the individual structure-based prediction tools. In addition, both the Sequence Coding Module and the Stand-alone Module maintain performance with only a 5% decrease of the Matthews correlation coefficient when the integrated online tools are unavailable. iStable 2.0 is available at http://ncblab.nchu.edu.tw/iStable2.

PClass: Protein Quaternary Structure Classification by Using Bootstrapping Strategy as Model Selection.

Protein quaternary structure complex is also known as a multimer, which plays an important role in a cell. The dimer structure of transcription factors is involved in gene regulation, but the trimer structure of virus-infection-associated glycoproteins is related to the human immunodeficiency virus. The classification of the protein quaternary structure complex for the post-genome era of proteomics research will be of great help. Classification systems among protein quaternary structures have not been widely developed. Therefore, we designed the architecture of a two-layer machine learning technique in this study, and developed the classification system PClass. The protein quaternary structure of the complex is divided into five categories, namely, monomer, dimer, trimer, tetramer, and other subunit classes. In the framework of the bootstrap method with a support vector machine, we propose a new model selection method. Each type of complex is classified based on sequences, entropy, and accessible surface area, thereby generating a plurality of feature modules. Subsequently, the optimal model of effectiveness is selected as each kind of complex feature module. In this stage, the optimal performance can reach as high as 70% of Matthews correlation coefficient (MCC). The second layer of construction combines the first-layer module to integrate mechanisms and the use of six machine learning methods to improve the prediction performance. This system can be improved over 10% in MCC. Finally, we analyzed the performance of our classification system using transcription factors in dimer structure and virus-infection-associated glycoprotein in trimer structure. PClass is available via a web interface at http://predictor.nchu.edu.tw/PClass/.