How to predict transmembrane protein topology?

Cornelius Krasel krasel at
Mon Oct 2 15:29:15 EST 1995

Terence (bclong at wrote:
> 	I often read in journals that a certain transmembrane topology is
> determined/predicted for a certain transmemnrane protein. How is this done?
> Is this done thru some commercial/public domain software? Or is it just by
> eyeballing how many hydrophobic segment there?

One of the most popular algorithms to determine hydrophobic segments is the
one by Kyte & Doolittle (JMB, published in the Seventies, I think), although
there are almost countless other algorithms to delineate hydrophobic
stretches of amino acids, I've been told.

To find out which part of the protein is on the "inside", one would probably
apply Gunnar von Heijne's "positive inside" rule (sorry, no reference at

So much for the prediction. Determination can be achieved by immunoreactivity
with certain antibodies (the epitope of which must be known, obviously);
insertion of tags; alkaline phosphatase fusion proteins (only in E. coli).


/* Cornelius Krasel, U Wuerzburg, Dept. of Pharmacology, Versbacher Str. 9 */
/* D-97078 Wuerzburg, Germany        email: phak004 at */
/* "Science is the game we play with God to find out what His rules are."  */

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