[gmx-users] [gmx-user] RMSD analysis of protein-ligand complex
Justin Lemkul
jalemkul at vt.edu
Thu Dec 26 17:36:56 CET 2019
On Thu, Dec 26, 2019 at 9:41 AM Quin K <profiles.ke at gmail.com> wrote:
> Thank you!
> I noted that there are two options called
> Guess bond orders from connectivity
> Include parameters that are already in CGenFF
> In the parachem website.
> Would checking these specially the second one would fix some of these
> problems?
No. Work with the topology you have. The second option also has nothing to
do with parameter assignment and will lead to duplicate parameter errors
later.
-Justin
> I have not used these options.
>
> Regards!
>
> On Thu, Dec 26, 2019 at 6:54 PM Justin Lemkul <jalemkul at vt.edu> wrote:
>
> >
> >
> > On 12/26/19 9:05 AM, Quin K wrote:
> > > Thank you!
> > > This is the output I got from parachem.
> > >
> >
> https://docs.google.com/document/d/180rWUj4XE-_OFBCVPsJajohNRKUYIClcP_V3cOer5qw/view
> > > Can this be used as it is?
> > >
> > > I used it as it is and did not validate or optimized further, could
> that
> > be
> > > the reason why ligand got detached from binding site during MD
> > simulation?
> >
> > Possibly. The charge and dihedral penalties are not low enough to be
> > considered sufficient without explicit validation using QM water
> > interaction energy and a 1-D potential energy surface around the
> > (potentially) problematic dihedral. It may be that the topology is fine,
> > but as the header says, penalties between 10-50 cannot be trusted
> > without proving the parameters are OK.
> >
> > -Justin
> >
> > > Thanks in advance!
> > > Regards
> > > Q
> > >
> > > On Wed, Dec 18, 2019 at 1:23 PM Justin Lemkul <jalemkul at vt.edu> wrote:
> > >
> > >>
> > >> On 12/18/19 6:40 AM, Quin K wrote:
> > >>> I generated ligand topology using parachem website, I didn't do any
> > >>> adjustments after, just used it as it is.
> > >> What do the penalty scores tell you about the quality of the
> parameters?
> > >>
> > >> -Justin
> > >>
> > >>> On Tue, 17 Dec 2019, 1:11 pm Justin Lemkul, <jalemkul at vt.edu> wrote:
> > >>>
> > >>>> On 12/15/19 1:18 PM, Quin K wrote:
> > >>>>> Hi
> > >>>>> Thank you!!!
> > >>>>>
> > >>>>> Let's say during restraining of ligand, if I increased the -fc
> value
> > >> to
> > >>>>> 10000 (i had 1000) or higher and equilibrated it for longer time
> > like 1
> > >>>> or
> > >>>>> 2 ns (I had 100ps), would it help?
> > >>>> Possibly.
> > >>>>
> > >>>>> Also would restraining the protein and ligand independently help?
> > >>>>> Or is generating a better ligand topology the only way to solve
> this
> > >>>> issue?
> > >>>>
> > >>>> It depends on how you validated the ligand topology. Do you have
> > >>>> evidence that it is of sufficiently high quality?
> > >>>>
> > >>>> -Justin
> > >>>>
> > >>>>> Thanks in advance.
> > >>>>> Regards
> > >>>>>
> > >>>>> On Sun, Dec 15, 2019 at 11:07 PM Justin Lemkul <jalemkul at vt.edu>
> > >> wrote:
> > >>>>>> On 12/15/19 11:47 AM, Quin K wrote:
> > >>>>>>> Hi All,
> > >>>>>>>
> > >>>>>>> Further to following email, i just noted that the ligand has
> > detached
> > >>>>>> from
> > >>>>>>> binding site.
> > >>>>>>> Is there a way to prevent this from happening?
> > >>>>>>> It happened to me once before with the same complex.
> > >>>>>> If the ligand is dissociating on a time scale that it shouldn't
> > (e.g.
> > >>>>>> you expect it should stay bound), that suggests the ligand
> topology
> > is
> > >>>>>> insufficiently accurate, arising from interactions with the
> protein
> > >> that
> > >>>>>> are too weak and/or interactions with water that are too strong.
> > >>>>>>
> > >>>>>>> Doesn't boundary conditions prevent ligand from detaching from
> > >> binding
> > >>>>>> site
> > >>>>>>> in protein during MD simulation?
> > >>>>>> No, PBC does not do this. A periodic system contains copies of
> > >> whatever
> > >>>>>> is happening in the central image.
> > >>>>>>
> > >>>>>> -Justin
> > >>>>>>
> > >>>>>> --
> > >>>>>> ==================================================
> > >>>>>>
> > >>>>>> Justin A. Lemkul, Ph.D.
> > >>>>>> Assistant Professor
> > >>>>>> Office: 301 Fralin Hall
> > >>>>>> Lab: 303 Engel Hall
> > >>>>>>
> > >>>>>> Virginia Tech Department of Biochemistry
> > >>>>>> 340 West Campus Dr.
> > >>>>>> Blacksburg, VA 24061
> > >>>>>>
> > >>>>>> jalemkul at vt.edu | (540) 231-3129
> > >>>>>> http://www.thelemkullab.com
> > >>>>>>
> > >>>>>> ==================================================
> > >>>>>>
> > >>>>>> --
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> > >>>> Justin A. Lemkul, Ph.D.
> > >>>> Assistant Professor
> > >>>> Office: 301 Fralin Hall
> > >>>> Lab: 303 Engel Hall
> > >>>>
> > >>>> Virginia Tech Department of Biochemistry
> > >>>> 340 West Campus Dr.
> > >>>> Blacksburg, VA 24061
> > >>>>
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> > >>>> http://www.thelemkullab.com
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> > >> --
> > >> ==================================================
> > >>
> > >> Justin A. Lemkul, Ph.D.
> > >> Assistant Professor
> > >> Office: 301 Fralin Hall
> > >> Lab: 303 Engel Hall
> > >>
> > >> Virginia Tech Department of Biochemistry
> > >> 340 West Campus Dr.
> > >> Blacksburg, VA 24061
> > >>
> > >> jalemkul at vt.edu | (540) 231-3129
> > >> http://www.thelemkullab.com
> > >>
> > >> ==================================================
> > >>
> > >> --
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> >
> > --
> > ==================================================
> >
> > Justin A. Lemkul, Ph.D.
> > Assistant Professor
> > Office: 301 Fralin Hall
> > Lab: 303 Engel Hall
> >
> > Virginia Tech Department of Biochemistry
> > 340 West Campus Dr.
> > Blacksburg, VA 24061
> >
> > jalemkul at vt.edu | (540) 231-3129
> > http://www.thelemkullab.com
> >
> > ==================================================
> >
> > --
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--
==========================================
Justin A. Lemkul, Ph.D.
Assistant Professor
Office: 301 Fralin Hall
Lab: 303 Engel Hall
Virginia Tech Department of Biochemistry
340 West Campus Dr.
Blacksburg, VA 24061
jalemkul at vt.edu | (540) 231-3129
http://www.thelemkullab.com
==========================================
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