Node-Weighted Amino Acid Network Strategy for Characterization and Identification of Protein Functional Residues

The study of functional residues (FRs) is essential for understanding protein functions and biological processes. The amino acid network (AAN) has become an emerging paradigm for studying FRs during the past decade. Current AAN models ignore the heterogeneity of nodes and treat amino acids in the AAN as the same. However, the properties of each amino acid node are of fundamental importance. We here proposed a node-weighted AAN strategy termed the node-weighted amino acid contact energy network (NACEN) to characterize and predict three types of FRs, namely, hot spots, catalytic residues, and allosteric residues. We first constructed NACENs with their nodes weighted based on structural, sequence, physicochemical, and dynamical properties of the amino acids and then characterized the FRs with the NACEN parameters. We finally built machine learning predictors to identify each type of FR. The results revealed that residues characterized with NACEN parameters are more distinguishable between FRs and non-FRs tha...