30 December 2010

Flattening fragments

If you want to visualize and manipulate crystallographic data there are plenty of options, such as PyMOL and OpenAstexViewer. However, powerful molecular graphics programs such as these have a learning curve associated with them, and sometimes it’s nice to get a simple two-dimensional image. In the December issue of ACS Medicinal Chemistry Letters, Katrin Stierand and Matthias Rarey describe software they’ve developed to do this.

PoseView, which can be used online free of charge, automatically generates a two-dimensional view of a protein-ligand complex and labels five different types of interactions: hydrogen bonds, metal interactions, pi-cation interactions, pi-pi stacking, and undirected hydrophobic contacts.

The researchers tested their software by using it to draw nearly every protein-ligand interaction in the Protein Data Bank (PDB) in which the ligand has 5 to 80 atoms, excluding crystallization buffer components and things like heme or iron-sulfur clusters. For the remaining 200,000+ complexes, PoseView successfully generated plots for 85% of them; interestingly, most of the failures resulted because there were no apparent interactions between the protein and “ligand.” Of the successes, 80% produced high-quality figures in which there were no overlapping features – not bad considering the challenge of reducing a three-dimensional model to a two-dimensional image.

The paper includes some interesting data about protein-ligand complexes in general. For example, over 90% of complexes in the PDB have less than 11 directed interactions (ie, interactions other than hydrophobic contacts), with the largest number having only a single directed interaction. It would be interesting to see how these statistics apply to fragment-sized ligands.

PoseView is incredibly easy to use: just enter a pdb code or upload a structure, and the program spits out an image. I tried it on the very first fragment I discovered, and the result looks quite attractive:

Of course, there is always room for improvement: for example, it would be nice if you could change fonts or colors (the output is a pdf). Still, this is a useful addition to the toolbox of modeling programs.

And with this post, Practical Fragments says goodbye to 2010 and wishes everyone a happy holiday season. We look forward to more exciting developments in 2011 – and if we miss any, please send them our way!

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