Hi, I was conducting few physochemical analysis for my target protein and found out that the protein located in the transmembrane region. Usually, transmembrane protein are hydrophobic and will yield positive GRAVY value. However, after further analysis, it was revealed that my protein of interest was slightly hydrophilic with GRAVY value of -0.2. How is this possible?
Dear Fatin Safiudin ,
Be careful with the interpretation of the GRAVY value. The method is more equipped to identify potential transmembrane sequences. The original paper by Kyte & Doolittle clearly indicates this. When it comes to your observation, in Table 6 you can see that they found an experimentally identified membrane protein with a GRAVY score of -0.22:Article A Simple Method for Displaying the Hydropathic Character of a Protein
(in Google Scholar you can find a version which you can upload).There are numerous places where the use of the GRAVY score is discussed. See for an interesting finding and discussion about the GRAVY score (of the total sequence of a protein) that describes (as discussed on page 5 and 6) that only 9.76% of the TM proteins had a positive GRAVY score here: Article Separation and identification of mouse liver membrane protei...
The thing is that a membrane protein can have large stretches that are located outside the membrane and have one or two TM sequences which anchor it in the membrane. This means that overall, the GRAVY can be negative.An elegant approach to distinguish between a soluble, peripheral and membrane protein is the so-called Eisenberg approach. See for a user-friendly Heliquest generated Eisenberg plot approach: Article New User-Friendly Approach to Obtain an Eisenberg Plot and I...
But back to your question. Yes, a membrane protein can have a low GRAVY score.
Best regards.
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