WG/GW domains recruit ARGONAUTE (AGO) proteins to distinct silencing effector complexes using combinations of just two amino acids: tryptophan (W) and glycine (G), forming a wide arsenal of highly simplified interaction surfaces. These unstructured domains exhibit very low sequence identity and excessive length polymorphism, which makes identification of new AGO-binding proteins a challenging task as they escape detection with standard sequence comparison-based methods (e.g., BLAST, HMMER).In this chapter, we explain the use of tools for prediction of AGO-binding WG/GW domains in protein sequences. We also show how to computationally explore an up-to-date information about AGO-interacting proteins and discover new properties of WG/GW domains. Finally, we encourage readers to explore the game-like web application for in silico designing/modifying AGO-binding sequences as well as modeling mutagenesis experiments and predicting their potential effect on AGO-binding activity.
Keywords: AGO-binding domain; ARGONAUTE; Protein domain; Sequence analysis; WG/GW domain; Web application.