Subject: Prediction of Protein Crystallinity (summary)

From: [email-masked] (Gary Meier)
Date: Thu, 29 Sep 1994 16:06:43 -0600

About a week ago, I posted the following question(s) to the net and
promised to summarize replies.  I'm repeating the question today, as I'm
still hoping to receive more information on the subject.  The replies I've
received to date are summarized below the question.

        My Original Question:

Are there any algorithms, or rules of thumb, for estimating from a protein
sequence the likelihood that the protein will crystallize?  Can we study
patterns of hydrophobic residues or some other feature(s) contained in the
sequence and predict if the protein will crystallize?  If so, can we
suggest reasonable crystallization conditions to try?  How  might
conditions differ if crystallization of a protein dimer is desired?

Also, how might selection of a ligand for co-crystallization affect the
odds of crystallization success?  Is the highest affinity ligand
necessarily the best choice, or are there good reasons for selecting a
highly crystalline ligand, more hydrophobic ligand, etc.?

        Summary of Replies:     (Thanks to all who responded)

The first condition is that units pack identically
in a lattice.  This precludes diffraction study of
e.g. any protein existing in a variety of native
conformations in any specific state, thereby inviting
the conclusion that all proteins exist in only a
single native conformation in any specific state
;-).  Of course, "disordered regions" are sometimes
identified.  I'd be delighted to be enlightened
further about this issue.

A second corollary of this restriction is that inter-chain
"packing" forces are weak, inasmuch as strong interchain
interactions on a large molecule are likely to link
in "degenerate" fashion (non-uniquely?), thereby mediating
a non-crystalline agglomeration.  I think this problem
occurs with some exposed beta-sheet structures.

Note, however, that interchain attractions must be great
enough to liberate heat upon crystallization sufficient
to compensate for the entraopy decrease of the crystalline
ordering.  Thus, a delicate balance!

I will look forward to other replies!  Thanks,

John

John Reissner         Pembroke State University     Pembroke NC  28372  USA
[email-masked]     vox: (910)521-6425    fax: (910)521-6649
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Just as a suggestion: there is the latest issue of Acta Cryst, Section D,
Vol.50, which deals with crystallization of biological macromolecules. But
I haven't in mind, if there are any articles about prediction starting from
the sequence. I would think, that the only information available from the
sequence is the pI and the overall/local hydrophobicity ( to be
crystallized with/without detergens).

Clemens
--

* Clemens Vonrhein             email:[email-masked] *
*                                                                         *
*         Institut f. Org. Chemie u. Biochemie                            *
*         Albertstr.21                                                    *
* D-79104 Freiburg i.Br. (Germany)                                        *
*  Tel.: 761/203-6061   FAX: 761/203-5987                                 *

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I do not know if this will be useful, but Sedzik had recently published a
guide on how to use variables from crystallization experiments in an
optimal way.

Sedzik. J., Archives of Biochemistry and Biophysics, Vol, 308, 2:342-8, 1994.

The paper describes a program called DESIGN developed to address the problem
of scarce resources and large amounts of protein needed for crystallization.

Thomas Nittoli
Dept. of Chemistry
State University of NY
Stony Brook, NY 11794-3400 USA

Phone: (516)632-7854   FAX: (516)632-7960
Internet: [email-masked]
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Gary Meier, Ph.D.                  Senior Research Computational Scientist
FMC Corporation,
Agricultural Chemical Group
Box 8
Princeton, NJ 08543               (609) 951-3448     ([email-masked])