wanting to use the membrane abinitio application, I'd really like to know how the "Mlipo" score is calculated. I assume also using the .lips4 file as input? And is the .lips4 file used for anything else? I could not find this piece of information in the manual/forum and also not in the paper describing the membrane low-res. application (Proteins 2006, 62:1010).
I would like to make systematic changes to the .lips4 file before the structure prediction, therefore this is a very important piece of information for me and I would greatly apreciate any help/hints or literature that I overlooked :)
In the code, look at file rosetta_source/src/core/scoring/methods/MembraneLipo.cc, function finalize_total_energy. I've asked the original authors for comment.
The Mlipo score is related to the difference in exposed surface area between residues predicted to be exposed and buried. But we use the number of neighbors within 10Å as our surface area measure. Many neighbors means small exposed surface area, and vice versa….
It is only the second column in the lips4 that is used. There residues are defined to be either buried (values < 0) or exposed (values > 0). We use the lips server to predict this and from that server we get six different phases for a given alpha helixes. The same residue can belong to different phases. That's why you'll see the same residue occurring more than once. For instance one residue might belong to the -0.5 and 0.5 phase, meaning it is partly buried and partly exposed, i.e on the side. In the scoring we sum up these values so we get one weight per residue, in the example we would have gotten weight 0. We then calculate a weighted average number of neighbors for the exposed and buried class, take the difference and return this value multiplied by the number of transmembrane helices (or the number of currently inserted transmembrane helices in the case of ab initio folding)
Björn Wallner IFM
Associate Professor Linköping University
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Thank you, both of you for your answers! ... I got the calculation of the Mlipo score now and it's good to know that the colunms 3&4 in the .lips4 file are not used by the membrane abinitio app, right?
Now, could you maybe also help me to find out & adjust the weighting factor of the Mlipo term in the total score? That would help me to see a clearer effect if I make changes in the lipo file.
Thank you for your help :)
These files appear to be used by membrane abinitio:
That's where the weights are set. Mlipo appears only in score_membrane, which appears to be the primary ab initio scorefunction, and has a weight of 1.