VMD-L Mailing List

From: Prof. Eddie (eackad_at_siue.edu)
Date: Wed Feb 03 2021 - 10:14:56 CST

Thanks for the tip! I'll do that.

On Thu, Jan 28, 2021 at 4:21 PM Peter Freddolino <petefred_at_umich.edu> wrote:

> Another possibility would just be to terminate your side chain of interest
> with a methyl group where the alpha carbon would be, and use that for
> parameterization. Either way, you'll almost certainly want to use the
> standard charmm parameters and charges for the backbone atoms rather than
> whatever you get via cgenff/fftk, keeping the new parameters only for the
> really new stuff. The protein backbone parameters are HIGHLY optimized and
> you don't want to mess with them.
> Best,
> Peter
>
> On Thu, Jan 28, 2021 at 5:11 PM Prof. Eddie <eackad_at_siue.edu> wrote:
>
>> Thank you! That worked to get it into cgenff. I guess I'll just use fftk
>> to optimized the parameters for this "terminated" residue and then remove
>> the backbone part.
>> Thanks all!
>>
>> On Thu, Jan 28, 2021 at 2:36 PM Smith, Harper E. <
>> smith.12510_at_buckeyemail.osu.edu> wrote:
>>
>>> Hi Eddie,
>>>
>>> There are N/C terminal patches you can apply to your residue. One idea
>>> might be to acetylate the N-terminus (patch ACE) and methylamidate the
>>> C-terminus (patch CT3).
>>>
>>> HTH,
>>> Harper
>>> ------------------------------
>>> *From:* owner-vmd-l_at_ks.uiuc.edu <owner-vmd-l_at_ks.uiuc.edu> on behalf of
>>> Prof. Eddie <eackad_at_siue.edu>
>>> *Sent:* Thursday, January 28, 2021 3:21 PM
>>> *To:* Peter Freddolino <petefred_at_umich.edu>
>>> *Cc:* Vmd l <vmd-l_at_ks.uiuc.edu>
>>> *Subject:* Re: vmd-l: novel residue creation and parameterization
>>>
>>> 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
>>>
>>
>>
>> --
>> _________________________________________________________
>> Edward Ackad, Ph.D
>> <https://urldefense.com/v3/__http://www.siue.edu/*7Eeackad__;JQ!!DZ3fjg!pRQ21qDFHiBfacPd9erMf3TZEXoU-juJI4tN_IPQsy_RS02jDOMbewLSkzd-Ew6c3w$>
>> 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!rmNizMAALaADUhoJKqVspVBXOZVbONusGtD8t2cPbcEnPTSdfkQOZuMIpo5RwC9CYA$ >
Associate Professor of Physics
Computational Nanophotonics
Southern Illinois University Edwardsville
(618) 650-2390