Studying protein-ligand interactions using protein crystallography

Iain W. Mcnae, Daphne Kan, George Kontopidis, Alan Patterson, Paul Taylor, Liam Worrall, Malcolm D. Walkinshaw*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Protein X-ray crystallography is now a relatively high-throughput technique that plays a major role in structure-based drug design programs where the method of soaking small organic ligands into protein crystals is used to confirm or identify binding modes. In this review, we discuss some experimental approaches for 'soaking-in' ligands into protein crystals where the major problem is poor solubility of the ligand. We also provide examples showing how crystal soaking can be used as a technique for establishing ligand binding strength: Kc (the apparent ligand-protein dissociation constant in the crystal), which for some proteins at least, is found to be very similar to the solution Kd. Kinetic effects are also found to be important and the rate at which ligands soak into crystals is shown to vary by orders of magnitude from 10-1 to 107 s depending on the system.

Original languageEnglish
Pages (from-to)61-71
Number of pages11
JournalCrystallography reviews
Issue number1
Publication statusPublished - 1 Jan 2005

Keywords / Materials (for Non-textual outputs)

  • CDK2
  • Cyclin dependant kinase
  • Cyclophillin
  • Drug design
  • Elastase
  • Soaking


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