This practical is intended to introduce you to a number of publicly available web-based tools from the Structural Biology Department at Uppsala University that can be of use in validating ligands as they occur in complexes with macromolecules in the Protein Data Bank (PDB). In particular, you will make the acquaintance of:

1. EDS, the Uppsala Electron-Density Server.
2. HIC-Up, the Hetero-compound Information Centre in Uppsala.
3. ValLigURL, a server for analysis, comparison and validation of ligand structures.

You should have received reprints of the following papers (if not, you can have them e-mailed to you with the links below):

1. GJ Kleywegt & MR Harris, "ValLigURL: a server for ligand-structure comparison and validation", Acta Crystallographica, D63, 935-938 (2007). (Request reprint.)
2. GJ Kleywegt, "Crystallographic refinement of ligand complexes", Acta Crystallographica, D63, 94-100 (2007). (Request reprint.)
3. GJ Kleywegt, MR Harris, J Zou, TC Taylor, A Wählby & TA Jones, "The Uppsala Electron-Density Server", Acta Crystallographica, D60, 2240-2249 (2004). (Request reprint.)

Once you have finished this practical, you should be able to do the following for any ligand in the PDB that you encounter (for instance, while reading a paper about a complex of that ligand with a biomacromolecule):

• inspect the density for the ligand, and assess if the experimental crystallographic data supports the placement, orientation and conformation of the ligand.
• locate various kinds of information (chemical, biological, pharmacological, biochemical, crystallographic, etc.) about the ligand.
• get a rough idea of the quality of the ligand.
• compare the structure of the ligand to all other copies of that ligand in the PDB.

Throughout the practical you will encounter questions (in red font on a yellow background). Discuss these with your co-worker(s) and write down your answers (so your instructor can ask you to explain or defend them)! Some of the questions are optional - only try to answer these if you have lots of time, or if your instructor explicitly told you to. Finally, hover with your mouse over the image with the question marks ...

History ...

1. Practical by Gerard Kleywegt, Uppsala University.
   Developed for the 2008 EMBO course in Cambridge on "Computational Aspects of the Protein Target Selection, Protein Production Management and Structure Analysis Pipeline."