Computational Design of Ligand Binding Proteins

Volume 1414 of the series Methods in Molecular Biology pp 1-21


In silico Identification and Characterization of Protein-Ligand Binding Sites

  • Daniel Barry RocheAffiliated withInstitut de Biologie Computationnelle, LIRMM, CNRS, Université de MontpellierCentre de Recherche en Biologie cellulaire de Montpellier, CNRS-UMR 5237 Email author 
  • , Liam James McGuffinAffiliated withSchool of Biological Sciences, University of Reading

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Protein–ligand binding site prediction methods aim to predict, from amino acid sequence, protein–ligand interactions, putative ligands, and ligand binding site residues using either sequence information, structural information, or a combination of both. In silico characterization of protein–ligand interactions has become extremely important to help determine a protein’s functionality, as in vivo-based functional elucidation is unable to keep pace with the current growth of sequence databases. Additionally, in vitro biochemical functional elucidation is time-consuming, costly, and may not be feasible for large-scale analysis, such as drug discovery. Thus, in silico prediction of protein–ligand interactions must be utilized to aid in functional elucidation. Here, we briefly discuss protein function prediction, prediction of protein–ligand interactions, the Critical Assessment of Techniques for Protein Structure Prediction (CASP) and the Continuous Automated EvaluatiOn (CAMEO) competitions, along with their role in shaping the field. We also discuss, in detail, our cutting-edge web-server method, FunFOLD for the structurally informed prediction of protein–ligand interactions. Furthermore, we provide a step-by-step guide on using the FunFOLD web server and FunFOLD3 downloadable application, along with some real world examples, where the FunFOLD methods have been used to aid functional elucidation.

Key words

Protein function prediction Protein–ligand interactions Binding site residue prediction Biochemical functional elucidation Critical Assessment of Techniques for Protein Structure Prediction (CASP) Continuous Automated EvaluatiOn (CAMEO) Protein structure prediction Structure-based function prediction Quality assessment of protein–ligand binding site predictions