[gmx-users] Disulfide bridge formation between A and B state

[Jochen Hub]

Hi Berk,

thanks a lot for the comment.

Actually I have found a solution which is good enough for what I am 
planing to do. I have placed a dummy onto the sulfur which is turned on 
while the sulfur is tuned off. And I switch on a bond between the dummys 
when switching from A to B. Then I have added all the necessary 
exclusions and pairs between the dummy and the nearby atoms, and the new 
angles and dihedrals due to the S-S bond.

The only issue which is now not exact are the 1-4 coulomb interactions 
of the dummies in the B state. They are computed completely instead of 
being scaled down by 1.2. So for a real FEP calculation that might be a 
problem, but for me it is fine.

Cheers,

Jochen


Berk Hess wrote:
> Hi,
>
> I would say that it is very uncommon to form a bond during free energy 
> calculations.
>
> To make this work easily we would need to introduce a pair interaction 
> with all parameters explicit
> that can be perturbed.
>
> For the moment you should be able to get it to work using tabulated 
> bonded interactions.
> The only thing that is not supported through that are soft-core 
> interactions, but I guess
> those will not be necessary for 1-4 interactions.
>
> Berk
>
> > Date: Fri, 20 Nov 2009 14:01:28 +0100
> > From: jochen at xray.bmc.uu.se
> > To: gmx-users at gromacs.org
> > Subject: [gmx-users] Disulfide bridge formation between A and B state
> >
> > Hi,
> >
> > I have yesterday already started a topic, but I think I was a bit
> > unclear about what is the problem.
> >
> > I want to have a disulfide bridge in the B state, but not in the A
> > state. And I have not found a way to get the Coulomb interaction 
> between
> > the two sulfurs (and other nearby atoms) right in the A and in the B 
> state.
> >
> > A-state:
> > ...C-S-H H-S-C...
> >
> > B-state:
> > ... C-S-S-C
> > | |
> > H H (where these two H are dummies in B)
> >
> > To close the S-S bond smoothly by going from lambda=0 to 1, I have 
> added
> > a bond type 6 (harmonic potential)
> > [ bonds ]
> > S-nr S-nr 6 b0 k
> > and, a bond type 5 (connection without interaction)
> > S-nr Snr 5
> > That is required since otherwise, I will have full LJ interaction in B
> > state between, e.g. between the two sulfurs. To have correct LJ
> > interaction in A, I have added pairs between all required atoms, so the
> > LJ should be fine.
> >
> > But what about the charges? If I have a connection between, e.g.,
> > sulfur1 and sulfur2, I will never have a coulomb interaction. The
> > problem seems that there is no way to scale a coulomb interaction
> > between two atoms between A and B. There is a pair type 2, that
> > apparently allows to add 1-4 charge interactions, but the parameters
> > cannot be scaled between state A and B (manual table 5.4).
> >
> > I feel that forming a bond with the FEP should be more or less common
> > thing, that's why I am surprised that there seems to be no solution for
> > that. Or am I missing something here?
> >
> > Any ideas?
> >
> > Thanks a lot,
> >
> > Jochen
> >
> >
> >
> > --
> > ---------------------------------------------------
> > Dr. Jochen Hub
> > Molecular Biophysics group
> > Dept. of Cell & Molecular Biology
> > Uppsala University. Box 596, 75124 Uppsala, Sweden.
> > Phone: +46-18-4714451 Fax: +46-18-511755
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-- 
---------------------------------------------------
Dr. Jochen Hub
Molecular Biophysics group
Dept. of Cell & Molecular Biology
Uppsala University. Box 596, 75124 Uppsala, Sweden.
Phone: +46-18-4714451 Fax: +46-18-511755
---------------------------------------------------