Identification of Key Residues in Proteins Through Centrality Analysis and Flexibility Prediction with RINspector.

ABSTRACT

Protein structures inherently contain information that can be used to decipher their functions, but the exploitation of this knowledge is not trivial. We recently developed an app for the Cytoscape network visualization and analysis program, called RINspector, the goal of which is to integrate two different approaches that identify key residues in a protein structure or complex. The first approach consists of calculating centralities on a residue interaction network (RIN) generated from the three-dimensional structure; the second consists of predicting backbone flexibility and needs only the primary sequence. The identified residues are highly correlated with functional relevance and constitute a good set of targets for mutagenesis experiments. Here we present a protocol that details in a step-by-step fashion how to create a RIN from a structure and then calculate centralities and predict flexibilities. We also discuss how to understand and use the results of the analyses. © 2018 by John Wiley & Sons, Inc.