Protein informatics is a newer name for an already existing discipline. It encompasses the techniques used in bioinformatics and molecular modelling that are related to proteins. While bioinformatics is mainly concerned with the collection, organization, and analysis of biological data, molecular modelling is devoted to representation and manipulation of the structure of proteins. Protein informatics requires substantial prerequisites on computer science, mathematics, and molecular biology. The approach chosen here, allows a direct and rapid grasp on the subject starting from basic knowledge of algorithm design, calculus, linear algebra, and probability theory. This text provides the reader a comprehensive introduction to the field of protein informatics. The text emphasizes mathematical and computational methods to tackle the central problems of alignment, phylogenetic reconstruction, and prediction and sampling of protein structure.