Accounting for global protein deformability during protein-protein and protein-ligand docking

Andreas May, Martin Zacharias

Research output: Contribution to journalArticlepeer-review

103 Scopus citations


Computational docking methods are valuable tools aimed to simplify the costly process of drug development and improvement. Most current approaches assume a rigid receptor structure to allow virtual screening of large numbers of possible ligands and putative binding sites on a receptor molecule. However, inclusion of receptor flexibility can be of critical importance since binding of a ligand can lead to changes in the receptor protein conformation that are sterically necessary to accommodate a ligand. Recent approaches to efficiently account for receptor flexibility during docking simulations are reviewed. In particular, accounting efficiently for global conformational changes of the protein backbone during docking is a still challenging unsolved problem. An approximate method has recently been suggested that is based on relaxing the receptor conformation during docking in pre-calculated soft collective degrees of freedom (M. Zacharias, Rapid protein-ligand docking using soft modes from molecular dynamics simulations to account for protein deformability: binding of FK506 to FKBP, Proteins: Struct., Funct., Genet. 54 (2004) 759-767). Test applications on protein-protein docking and on docking the inhibitor staurosporine to the apo-form of cAMP-dependent protein kinase A catalytic domain indicate significant improvement of docking results compared to rigid docking at a very modest computational demand. Accounting for receptor conformational changes in pre-calculated global degrees of freedom might offer a promising route to improve systematic docking screening simulations.

Original languageEnglish
Pages (from-to)225-231
Number of pages7
JournalBiochimica et Biophysica Acta - Proteins and Proteomics
Issue number1-2
StatePublished - 30 Dec 2005
Externally publishedYes


  • Approximate normal mode
  • Docking minimization
  • Domain motion
  • Induced fit binding
  • Ligand-receptor interaction
  • Receptor flexibility


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