From: Prof. Eddie (eackad_at_siue.edu)
Date: Thu Jan 28 2021 - 14:21:13 CST

The novel residue attaches to the carbon alpha of the backbone just as any
sidechain so there is nothing funky there. But if I make a fragment of just
the sidechain to save then some bonds need to get left out and so this is
what causes the problem. If I include the backbone I have "dangling" bonds
there. If I try just the sidechain I have a dangling bond there. I don't
see how without inputting the complete protein I can avoid that, but I
can't see how using the whole protein is reasonable either. How can I give
cgenff something that doesn't have a dangling bond then? Do I have to
treat it as a ligand and add hydrogens to terminate say the backbone atoms
and then manually remove those from the topology file?
Thanks again for your help!
Eddie

On Thu, Jan 28, 2021 at 12:24 PM Peter Freddolino <petefred_at_umich.edu>
wrote:

> Hi Eddie,
> You certainly shouldn't be parameterizing the whole protein, only the new
> residue that you're trying to add. What is the chemistry of the attachment
> of your new component to the rest of the protein? Is it incorporated to the
> protein backbone in some way, or is it a modification attached to a side
> chain? The protein topologies are by design pretty modular, so what you
> just need to figure out is what is an appropriate attachment point beyond
> which you can treat your new component like any other part of the protein
> force field. Just for example, if you were trying to add a new amino acid,
> you would likely assume (unless the beta carbon had some really funky
> chemistry) that you can use the same backbone parameters as all other amino
> acids in the charmm forcefield, and then focus on parameterizing your
> fragment and its attachment to the alpha carbon.
> Best, Peter
>
>
> On Thu, Jan 28, 2021 at 12:32 PM Prof. Eddie <eackad_at_siue.edu> wrote:
>
>> Hello,
>> I'm not sure how to do that. Molfracture saves each residue in its own
>> mol2 file. Otherwise, I need to rename the whole protein to have 1 residue
>> name. Even then cgenff says I have a carbene and won't proceed (although
>> molfracture does not find anything which a large charge). Is there some
>> other way to write it?
>>
>> Also, do I need the whole protein put into cgenff or is there a way to
>> just have my novel residue and have it ignore the (incomplete) backbone? I
>> would just like to get the files so I can use fftk (which may also be
>> difficult if I need the whole protein in gaussian instead of just the novel
>> residue).
>> Thanks,
>> Eddie
>>
>>
>> On Wed, Jan 27, 2021 at 8:13 PM Peter Freddolino <petefred_at_umich.edu>
>> wrote:
>>
>>> Doesn't the cgenff server take mol2 files as a possible input? VMD can
>>> write these. You'll want to make sure you have all of the bonds set
>>> properly before saving so that that information propagates.
>>> Best,
>>> Peter
>>>
>>> On Wed, Jan 27, 2021 at 7:30 PM Prof. Eddie <eackad_at_siue.edu> wrote:
>>>
>>>> Thanks all. It seems using the newest molfracture with vmd1.9.4 removes
>>>> the error and the peptide bonds are preseved.
>>>>
>>>> That said, I still cannot get an STR file since the cgenff server
>>>> complains about both the whole protein or the single modified residue so I
>>>> still cannot get fftk to start optimizing the structure. Does vmd have any
>>>> other way I can create an str file for fftk besides the cgenff server?
>>>>
>>>> Thanks!
>>>> Eddie
>>>> BTW, when the residue is submitted alone it complains "...attype
>>>> warning: carbon radical, carbocation or carbanion not supported;skipped
>>>> molecule. ......" and charmmgui asks for a topology and parameter file
>>>> for the residue so that's no help.
>>>>
>>>>
>>>> On Wed, Jan 27, 2021 at 12:01 PM Vermaas, Josh <vermaasj_at_msu.edu>
>>>> wrote:
>>>>
>>>>> Hi Eddie,
>>>>>
>>>>>
>>>>>
>>>>> I’m betting that the topology is missing the peptide bonds in the
>>>>> bond, improper, and cmap declarations in the topology file. If you look at
>>>>> a standard protein topology file, you’ll see entries like: “BOND C +N”,
>>>>> which tells psfgen about the bond between the C atom and the N atom for the
>>>>> next residue. Similar entries typically exist for impropers and CMAP terms,
>>>>> and molefacture won’t make them by default.
>>>>>
>>>>>
>>>>>
>>>>> Does a simple psfgen script work?
>>>>>
>>>>>
>>>>>
>>>>> package require psfgen
>>>>>
>>>>> topology blah.top
>>>>>
>>>>> segment S {
>>>>>
>>>>> residue 1 XXX
>>>>>
>>>>> }
>>>>>
>>>>> #add some initial coordinates here from the pdb you get out of
>>>>> molefacture
>>>>>
>>>>>
>>>>>
>>>>> regenerate angles dihedrals
>>>>>
>>>>> guesscoord
>>>>>
>>>>> writepsf tmp.psf
>>>>>
>>>>>
>>>>>
>>>>> -Josh
>>>>>
>>>>>
>>>>>
>>>>>
>>>>>
>>>>> *From: *<owner-vmd-l_at_ks.uiuc.edu> on behalf of "Prof. Eddie" <
>>>>> eackad_at_siue.edu>
>>>>> *Reply-To: *"eackad_at_siue.edu" <eackad_at_siue.edu>
>>>>> *Date: *Wednesday, January 27, 2021 at 10:15 AM
>>>>> *To: *Vmd l <vmd-l_at_ks.uiuc.edu>
>>>>> *Subject: *vmd-l: novel residue creation and parameterization
>>>>>
>>>>>
>>>>>
>>>>> Hello,
>>>>>
>>>>> I have a protein and I'd like to mutate one of the residues to a large
>>>>> novel compound (a progesterone analog). I need the new residue to be bonded
>>>>> to the backbone. I think I have two issues.
>>>>>
>>>>> 1) I was able to create the new residue using molfracture. But once I
>>>>> exited and applied it to the larger structure it removed the peptide bond
>>>>> to the neighboring residue. I had to load the whole protein into
>>>>> molfracture to recreate the peptide bonds with the neighboring residues.
>>>>> However, I just gave the default atom types and did not run any of
>>>>> molfractures tools so the structure is not optimized.
>>>>>
>>>>> 2) I think I need to use fftk to now parameterize the residue but to
>>>>> create a psf I get failures of psfgen since it says my residue type (named
>>>>> XXX) is unknown. I thought that would invoke the paratools screen so I'd at
>>>>> least have the psf to start fftk. How can I get the psf?
>>>>>
>>>>>
>>>>>
>>>>> I appreciate any help. Most of the tutorials I've found have been for
>>>>> ligands (not bonded) or are direct edits to the parameter file since the
>>>>> novel structure is a small change. I'd like to do this more than once and
>>>>> so I'd like to know how to do it well.
>>>>>
>>>>> Thanks,
>>>>> Eddie
>>>>>
>>>>>
>>>>>
>>>>> --
>>>>>
>>>>> _________________________________________________________
>>>>> Edward Ackad, Ph.D
>>>>> <https://urldefense.com/v3/__http:/www.siue.edu/*7Eeackad__;JQ!!DZ3fjg!rqOLhm10ppn4K6XaJmAUON8FQtS_yDlQidgmGuMmAFBCVpARoeLBTrTciXaj7IIQPQ$>
>>>>> Associate Professor of Physics
>>>>> Computational Nanophotonics
>>>>> Southern Illinois University Edwardsville
>>>>> (618) 650-2390
>>>>>
>>>>
>>>>
>>>> --
>>>> _________________________________________________________
>>>> Edward Ackad, Ph.D
>>>> <https://urldefense.com/v3/__http://www.siue.edu/*7Eeackad__;JQ!!DZ3fjg!r5H2yZmtWQ9e6mGhBDKQu7hZXAgCA_K1dTnEeTEam2sgLCFLCqof0f9csgsq_PLE0w$>
>>>> Associate Professor of Physics
>>>> Computational Nanophotonics
>>>> Southern Illinois University Edwardsville
>>>> (618) 650-2390
>>>>
>>>
>>
>> --
>> _________________________________________________________
>> Edward Ackad, Ph.D
>> <https://urldefense.com/v3/__http://www.siue.edu/*7Eeackad__;JQ!!DZ3fjg!sSBpn5YJnqidDOYbRGzktV95oW_ghLXFz7nutMjE95Y7BYt1mAvDxV9wpRCbQKiEEw$>
>> Associate Professor of Physics
>> Computational Nanophotonics
>> Southern Illinois University Edwardsville
>> (618) 650-2390
>>
>

-- 
_________________________________________________________
Edward Ackad, Ph.D <https://urldefense.com/v3/__http://www.siue.edu/*7Eeackad__;JQ!!DZ3fjg!vgXwHoaPNb-mbp8Jn-Kuh1Y3IMgXAk5xKbGZnXx5wP7wnK6frjiWNWKdoI74XHheyg$ >
Associate Professor of Physics
Computational Nanophotonics
Southern Illinois University Edwardsville
(618) 650-2390