Identification of Hot Spots in Protein Structures Using Gaussian Network Model and Gaussian Naive Bayes.

Residue fluctuations in protein structures have been shown to be highly associated with various protein functions. Gaussian network model (GNM), a simple representative coarse-grained model, was widely adopted to reveal function-related protein dynamics. We directly utilized the high frequency modes generated by GNM and further performed Gaussian Naive Bayes (GNB) to identify hot spot residues. Two coding schemes about the feature vectors were implemented with varying distance cutoffs for GNM and sliding window sizes for GNB based on tenfold cross validations: one by using only a single high mode and the other by combining multiple modes with the highest frequency. Our proposed methods outperformed the previous work that did not directly utilize the high frequency modes generated by GNM, with regard to overall performance evaluated using F1 measure. Moreover, we found that inclusion of more high frequency modes for a GNB classifier can significantly improve the sensitivity. The present study provided additional valuable insights into the relation between the hot spots and the residue fluctuations.