Protein domain identification methods and online resources

Protein domains are the basic units of proteins that can fold, function, and evolve independently. Knowledge of protein domains is critical for protein classification, understanding their biological functions, annotating their evolutionary mechanisms and protein design. Thus, over the past two decades, a number of protein domain identification approaches have been developed, and a variety of protein domain databases have also been constructed. This review divides protein domain prediction methods into two categories, namely sequence-based and structure-based. These methods are introduced in detail, and their advantages and limitations are compared. Furthermore, this review also provides a comprehensive overview of popular online protein domain sequence and structure databases. Finally, we discuss potential improvements of these prediction methods.