Fr-TM-align inquiry

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Fr-TM-align inquiry

Post by kelven.rahy »


I am currently working on a project at the Lebanese American University where we're investigating new therapeutic options to be used against Leishmania tropica, the causing agent of leishmaniasis. One of the most promising approaches is the reposition of FDA-approved anti-leishmaniasis drugs. For that, we are trying to provide insight into the mechanism of action of those drugs.

The initial target protein (within other organisms such as Sarcoptes scabiei) is well known. Therefore, we aim to use tools to find structural similarities between the original binding site and the proteome of L. tropica. Afterward, the target will be validated via molecular docking and dynamic simulation.
For this reason, we chose fr-TM-align as it has been used for similar purposes in previous works. However, we are running into a few issues understanding how to run it to fit our purposes:
1. How do we give the tool a list of proteins to compare the structure of interest to? In the manual of the tool, it says, " If -a = 1, program compares a list of proteins against one target PDB" but in what format should the list be?
2. Should we only compare the binding pocket of the known protein to the entire proteome of L. tropica? Or should we compare the entire protein-drug complex to the L. tropica proteome?
3. When we get the numerous TM-scores (1 for each protein of the L. tropica proteome), how do we then identify the exact protein on which our drug acts? Is it the one with the highest TM-score?
4. After we identify the protein of interest from the L. tropica proteome, how do we visualize the exact pocket where the drug binds?

Thank you so much in advance for your help.