I've handled similar problems by (in my case for guanine N2) by defining a new
amber residue which lacks the appropriate hydrogen on N2. Then define another
"residue" which is the crosslink. Then, in leap, you will need to load the
prep (or other format) files for the modified guanine and for the crosslink
before you load up your starting structure PDB file. For some residues, you
may need to add definitions of missing force field paramters, also. You will
have to do some leap programming to get the sites of crosslinking correctly
defined (this will be a bonding site in addition to the head and tail sites).
Finally, be sure the guanine in your starting structure PDB file has the name
of the modified, not normal, guanine residue. Put the crosslink structure in
the PDB file (I used another "chain" for it). Finally, don't forget to make
the bonds to the crosslink in leap before you save the parmtop and crd files.
I generally followed the methods used to handle protein disulfule bonds.
Good luck.
Bud Dodson
On 2 Oct, Nicholson, James D Mr ARO wrote:
>
> On Tue, Oct 01, 2002, Nicholson, James D Mr ARO wrote:
>
>> I am modelling DNA with a cross-linking agent...
>>
>> What I did previously was to create a single residue which contained both
>> crosslinked residues and the linker. When I imported this into leap, leap
>> would correctly (for the most part) assign the atom types, but, I would
>> still need to manually repair missed bonds. Apparently, it doesn't much
>> like having a main chain that travels through the crosslink and out into
> the
>> other residue.
>>
>
> Imagine a double helix which contains two guanines that have been
> crosslinked with an N7 alkylating agent. When you read in the pdb file, you
> would expect to have two chains of DNA with a covalent bond between them via
> the linker. But what happens with xleap is that, instead of coupling O5's
> to the P from the preceeding residue and O3's to following residues on both
> chains, you end up with a complicated mess where one chain of the double
> helix has a link from O3' to P which skips the cross-linked residues
> entirely and the other chain has two connections for each O5'-P and O3'-P,
> one bond from each P to both of the O5' and O3' atoms.
>
> When leap reads a pdb file, it assigns amber atom types, charges, etc. by
> looking at the all_nucleic.lib, or whatever else you tell it to load with
> your leaprc. In my case, I used leap to create an OFF file with a new
> residue containing the crosslinked residues, and, I loaded it in my leaprc
> at startup.
>
> When I read in the entire double stranded DNA, leap tries to decide how to
> hook things up, especially since my pdb file doesn't have CONNECT cards,
> and, I'm not sure that leap would look at those even if they were there.
>
> Because I collapsed two guanine residues into one crosslinked residue, I was
> forced to rename half of the atoms (since a single residue must have unique
> atom names). That's why I find this behavior so weird; one O3 is named O3'
> and the other O3'5, yet both are connected to a P from the following residue
> on one of the strands. So, the erronious bonds are probably not based on
> the atom name.
>
> I attribute this sort of behaviour to the main chain/side chain paradigm
> which I see explicitly in the prmtop file and which I assume is used
> somewhere in the residue templates. This particular application has two
> "main chains" going through a single residue. And I think that's the
> problem.
>
> I am wondering if the residue templates can actually handle crosslinked DNA,
> and, I'm curious how sander handles disulfide links, since that poses the
> same problem. This is why I need to make manual changes to the structure.
>
>
> I get leap to generate a coordinate and topology file for sander via manual
> editing in leap, but, life would be easier if someone had a better way to do
> this.
>
> -Jim N.
>
>
>
>
--
M. L. Dodson bdodson_at_scms.utmb.edu
409-772-2178 FAX: 409-772-1790
Received on Thu Oct 03 2002 - 05:42:08 PDT
