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Recently, I had a chance to see a presentation about coupled_moves. There is hardly any information about it since the paper isn't published yet but I figured I would give it a try anyway. What I want to do is to redesign enzyme specificity for a new substrate . The problem is including rotamers library of my new substrate.
I created ligand rotamers with Frog2 (no acces to MOE or OpenEye) and created params files with:
"molfile_2_params.py rotamers.mol2 --conformers-in-one-file".
I've run into an issue getting the Matcher to work correctly. I have attached a log file with the error I am receiving (In this particular case I ran 3.4, but the error is the same for 3.5). The specific error is below:
ERROR: olditer != target_restype_index_map_.end()
ERROR:: Exit from: src/protocols/match/downstream/SecondaryMatcherToUpstreamResidue.cc line: 677
Any help would be greatly appreciated and if additional information is needed I would be glad to provide it.
I am doing enzyme design using a cst file and it seems that my constraint file is not properly defined.
I wish to define constraints such that the peptide N forms hydrogen bond with my ligand in the binding pocket. At the same time I would like this residue to be any other residue except proline. So i defined my cst as follows;
TEMPLATE:: ATOM_MAP: 1 atom_name: O8 P1 O7
TEMPLATE:: ATOM_MAP: 1 residue3: EY1
TEMPLATE:: ATOM_MAP: 2 atom_type: Nbb
TEMPLATE:: ATOM_MAP: 2 residue1: ACDEFGHIKLMNQRSTVWY
I have two questions concerning conformers in the enzyme design application:
1) Is hydrogen bonding calculated from heavy atoms only or should the conformer library contain, for example, hydroxyl groups with the hydrogen pointed in multiple directions for it to recognize when a hydrogen bond can be formed?
I see some strange behavior of enzyme design with ligand.
1) I have created a library of rotamers, set path to this library in params file (by PDB_ROTAMERS rotlib.pdb) and run enzyme design. But there is still only translation and rotation of rigid body in the active site and no using of the rotamer library. Only when I start with ligand structure with some clashes in the protein pdb file I can see optimization of of torsion angles of the ligand. Can you please explain how it works?
Is it possible to combine a flags file with command line arguments?
For example, something like this:
minimize_with_cst.linuxgccrelease -in:file:l min_pdb_file_list @flags_file
where flags_file contains additional options. Moreover, what is the effect of changing the order of command line arguments and flags files? Which takes precedence? That is, what is the difference between the above command and:
minimize_with_cst.linuxgccrelease @flags_file -in:file:l min_pdb_file_list
I would like to know whether the enzyme design protocol of Rosetta Suite can be used for increasing the catalytic activity of the enzyme. Here, I don't have to design the active site from scratch, but I need to design the active site in such a way so that the catalytic activity of the enzyme is increased. Also, the enzyme I am dealing with does not have data for transition state modeling for the substrate that I am dealing with.
Please provide you comments and suggestions