Bioinformatics Approaches for Understanding the Binding Affinity of Protein-Nucleic Acid Complexes

Methods Mol Biol. 2025:2867:315-330. doi: 10.1007/978-1-0716-4196-5_18.

Abstract

Protein-nucleic acid interactions are involved in various biological processes such as gene expression, replication, transcription, translation, and packaging. Understanding the recognition mechanism of the protein-nucleic acid complexes has been investigated from different perspectives, including the binding affinities of protein-DNA and protein-RNA complexes. Experimentally, protein-nucleic acid interactions are analyzed using X-ray crystallography, Isothermal Titration Calorimetry (ITC), DNA/RNA pull-down assays, DNA/RNA footprinting, and systematic evolution of ligands by exponential enrichment (SELEX). On the other hand, numerous databases and computational tools have been developed to study protein-nucleic acid complexes based on their binding sites, specific interactions between them, and binding affinity. In this chapter, we discuss various databases for protein-nucleic acid complex structures and the tools available to extract features from them. Further, we provide details on databases and prediction methods reported for exploring the binding affinity of protein-nucleic acid complexes along with important structure-based parameters, which govern the binding affinity.

Keywords: Binding affinity; Computational tools; Machine learning; Prediction methods; Protein-DNA complexes; Protein-RNA complexes.

MeSH terms

  • Binding Sites
  • Computational Biology* / methods
  • Crystallography, X-Ray
  • DNA / chemistry
  • DNA / metabolism
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / metabolism
  • Databases, Protein
  • Models, Molecular
  • Nucleic Acids / chemistry
  • Nucleic Acids / metabolism
  • Protein Binding*
  • Proteins / chemistry
  • Proteins / metabolism
  • RNA / chemistry
  • RNA / metabolism
  • RNA-Binding Proteins / chemistry
  • RNA-Binding Proteins / metabolism
  • Software

Substances

  • RNA
  • DNA
  • DNA-Binding Proteins
  • Nucleic Acids
  • RNA-Binding Proteins
  • Proteins