On Wed, May 29, 2019, Fabian Glaser wrote:
>
>Here, there is a PTR (phospho tyrosine) bound to the DNA through a C5’
>atom of DA. Tleap works, but the problem is that instead of making a bond
>between C5’ and OP1, it treats the DA as a terminal DA5 and adds a O5’
>(not present in the original pdb), which is wrong.
This, along with many other covalent modifications, is hard to model in
Amber. Here's what I would do, at least to start:
1. Load the PTR residue into xleap, and remove the hydrogen, and/or any
other atoms you don't need. Save under a different name.
2. Load DA5 into xleap, remove the O5', save under a new name (say DA6).
3. Modify the PdbResMap commands in your leaprc file to have leap use
DA6 as the 5' terminal adenosine rather than DA5.
4. Load your peptide/protein (with modified PTR) and DNA (with modified
DA5) into tleap, and use the bond command to add the cross-link between
PTR and DA6.
5. Modify by hand the charges in the PTR-DA6 region to be close to the
originals yet sum to the proper value; create a frcmod file to handle
any missing parameters.
Obviously: be prepared for hurdles, and check carefully that the
resulting prmtop file makes sense: parmed is a convenient way to examine
what you have.
I suggested the above approach because there is actually little
modification to standard residues, and I'm assuming/hoping that the
rotational profiles about the phosphate bond connecting DA and TYR are
similar to those in DNA itself. You could also treate the PTR-DA unit
as a novel residue, and start to parameterize that from scratch. But my
approach tries to make as few changes from standard protein/DNA force
fields as seems to make sense.
[There are efforts in the Amber community, led by Chris Schafmeister, to
completely revamp the way problems like this can be approached. But
that's still in development. I'd be interested in hearing how CHARMM or
GROMACS handles this sort of situation.]
...regards...dac
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Received on Thu May 30 2019 - 18:30:02 PDT
