[gmx-users] MD Error after adding a unnatural amio acid

[Mark Abraham]

> Hi Everyone,
>
> I once talked about this before and have new problem
> now. The new group was successfully attached to the
> protein, but problem comes during the process of MD.
> The error messages are always like the following with
> either new linkage broken or a neighboring Hydrogen
> flying away. Parameters except for partial charge are
> perfectly okay.

Well, actually these symptoms would tend to indicate that the new bonding
topology is not okay :-)

> The partial charges from HF
> calculations even made it worse, because of different
> scheme with gmx. I also tried to partition the new
> bulky group into small fragments when T-coupling, but
> did not help.

No, don't do that! In the vast majority of cases, you only want coupling
groups for (e.g.) surface, solvent, membrane, solute... not ions or other
little bits of stuff.

> I am wondering what the reasons are. Is
> the new group too big? What is the alternative to
> assign partial charge in gmx other than PRODRG?

The only reasonable method is to use a method similar to that which
designed the partial charges in the original force field, and then to
verify that those charges lead to reasonable simulations. Anything else
could be just so much fiction :-)

I would go back and assemble the topology of this thing piece by piece,
verifying at each stage that you have structural integrity... the stepwise
process will help you find where the real problem is, if an inspection of
the topology doesn't work in the first place!

Mark