Software

Software tool

We have worked hard the whole year to successfully redesigning ligand binding site of the Tar chemoreceptor with Rosetta software, according to protocol presented in "Rosetta and the Design of Ligand Binding Sites" (1). The work we have achieved can be expanded into other receptors and ligands, and can be a use for other researchers.

Our software tool offers the chance for fellow researcher to redesign ligand binding sites without inhibitions using our automation script. One can do so in two ways: on his local computer cluster server or online with the form below.
See the Rosetta page (link to rosetta page) for more explanations about the use of the software, and see the wet lab results of our designs.

Using local server

We supply a zip file for Linux system with all necessary scripts to successfully run the redesigning automatically. This scripts used only as a framework for working with Rosetta software, those you require to download and install: Rosetta software, BCL, OpenBable, Python and protein visualization program such as UCSF Chimera.

Install: Download our software to Linux operation system and unzip it on the server where you install the rest of the programs, in the same folder you wish to save your design work. Edit the path to the programs you just installed in 'runRosetta.sh' file, under the 'define variables' section, and you are ready to go.

Run the main program running the software is 'runRosetta.sh'. Run command for initial help:

./runRosetta.sh -h

The program divided into steps, according to the steps presented in the protocol protocol "Rosetta and the Design of Ligand Binding Sites" (1):

1. Pre-relax the protein. Run command:

./runRosetta -s 1 -r <receptor file name WITHOUT extension>

2. Prepare the ligand. Run command:

./runRosetta -s 2 -l <ligand file name WITHOUT extension>.

3. Place the ligand into the protein. This is the only step cannot be done automatically. Follow the instructions at the attached pdf file: "Step3.3-Place_the_ligand_into_the_protein.pdf"

4.Run Rosetta design. Run command:

./runRosetta -s 4 -l <ligand file name WITHOUT extension&gt -r <receptor file name WITHOUT extension&gt -m <number of output models>

5.Filter designs. Run command:

./runRosetta -s 5

The software offers default filtration, but this is not suitable for any ligand or receptor. The filters can be easily changed in one of the files '<results/interfaces>_metrics.config'. To remove a filter just delete it from the config file. To add a filter just add it in the same format as the others in the config file (the column number is the one in the respectively csv score file).

6. Run new cycle. Run command:

./runRosetta -s 6 -l <ligand file name WITHOUT extension> -r <receptor file name WITHOUT extension> -m <number of output

For more information see 'README.txt' file in the source zip file.

Using online form:

If you do not have access to Linux server, or you just not good with computers, we offer an easy way you can still get your redesigned ligand binding site. All you need to do is to fill out this form, and we will do the rest. We'll send you the result through the mail in the next few days.

Note that this is possible only for redesigning Tar ligand binding domain to bind your desired ligand. If you wish to redesign different receptor contact us through the mail: technionigem2016@gmail.com