Annotating Mutational Effects on Proteins and Protein Interactions: Designing Novel and Revisiting Existing Protocols

Methods Mol Biol. 2017:1550:235-260. doi: 10.1007/978-1-4939-6747-6_17.


In this review we describe a protocol to annotate the effects of missense mutations on proteins, their functions, stability, and binding. For this purpose we present a collection of the most comprehensive databases which store different types of sequencing data on missense mutations, we discuss their relationships, possible intersections, and unique features. Next, we suggest an annotation workflow using the state-of-the art methods and highlight their usability, advantages, and limitations for different cases. Finally, we address a particularly difficult problem of deciphering the molecular mechanisms of mutations on proteins and protein complexes to understand the origins and mechanisms of diseases.

Keywords: Databases; Mutations; Protein–protein interactions.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Binding Sites
  • Computational Biology / methods*
  • Databases, Genetic
  • Hydrogen Bonding
  • Models, Molecular
  • Molecular Sequence Annotation
  • Mutation*
  • Protein Binding
  • Protein Conformation
  • Protein Interaction Domains and Motifs
  • Protein Interaction Mapping / methods*
  • Protein Interaction Maps
  • Protein Stability
  • Proteins / chemistry
  • Proteins / genetics*
  • Proteins / metabolism*
  • Software*
  • Web Browser
  • Workflow


  • Proteins