Thanks to the explosion of genomic sequencing, coevolutionary analysis of protein sequences has gained great and ever-increasing popularity in the last decade, and it is currently an important and well-established tool in structural bioinformatics and computational biology. This chapter concisely introduces the theoretical foundation and the practical aspects of coevolutionary analysis, as well as discusses the molecular modeling strategies to exploit its results in the study of protein structure, dynamics, and interactions. We present here a complete pipeline from sequence extraction to contact prediction through two examples, focusing on the predictions of inter-residue contacts in a single protein domain and on the analysis of a multi-domain protein that undergoes functional, large-scale conformational transitions.
Keywords: Conformational dynamics; Direct-coupling analysis; Protein complexes; Residue contact prediction; Structural bioinformatics.