by Peter Nollert
October 14, 2009 07:52
Let's assume for a minute you're dealing with a protein of a certain sequence and you're wondering if the protein is crystallizable. The tool to assess crystallizability is: XtalPred. This is an online server that accepts amino acid sequences and provides you with:
• a comparison of protein features with corresponding distribution from the TargetDB
• summary features with crystallization problem areas
• prediction of ligands and
• lists close homologs that are more likely to crystallize.
The algorithms used are described in this paper. There's also a related blog post about the biggest Secret in crystallography here.
How about taking XtalPred for a test drive? Let's make it simple and use Lysozyme as an example. There are many conditions under which Hen Egg white Lysozyme crystallizes - it's a great workhorse for test-crystallizations. The PDB gives you 1151 'Structure Hits' when searching for Lysozyme.
OK, let's take the amino acid sequence of Hen Egg white Lysozyme (P00698), remove the leader sequence and submit it to XtalPred.
XtalPred input page with Lysozyme sequence inserted.
Here's what you get:
XtalPred output page with results displayed in tabular form
OK - Xtal pred finds the target ID and lots of other info - even that there are 516 homologs available in the PDB. But it classifies Lysozyme into the red crystallization class: "Difficult"??? A poor grade of five on a scale of 1 (optimal) to 6 (very difficult).
Come on guys - Lysozyme, difficult?
Lysozyme cystallizes easily! Check out this paper from 1946, reporting on Lysozyme crystallization from egg white (check out the nice historical photographs of Lysozyme crystals).
Lysozyme crystals even grow when triggered with a flash of light. Lysozyme crystallization is indeed fool proof - I've successfully taught a physicist how to crystallize Lysozyme (a theoretical physisists who'd never touched a pipettor).
I guess that if you get an XtalPred result in the green = 'optimal' zone you've got crystals in your vial once you go back to the bench.
Peter