Effects of Mutations in Proteins on Their Interactions

Mutation processes introduce changes in the genome, which, when occurring in protein-coding sequences, result in alterations of the amino acid sequences of the corresponding expressed proteins. Genetic variations can come in many different forms and result in complex effect cascades. The most common genetic variants are single-nucleotide variants that, when they are non-synonymous, lead to a substitution of a single amino acid in a protein. Such substitutions are often functionally neutral, but in some cases may impact binding affinity of an interaction between the affected protein and an interaction partner. Many computational methods have been developed to comprehend, analyze, and predict these events. Some of them are specialized for particular cases (protein types or phenotypes), and others are for general purposes. In this chapter, we provide an overview of these methods and some guidelines on how to choose the correct method for different scenarios.