On Wed, Mar 22, 2023, Steinbrecher, Thomas via AMBER wrote:
>
>my experience here may be outdated, but the stability issues you mention
>are (or were some years ago) typical for MD simulations of protonated
>phosphates. As you describe, the imbalance between electrostatics and vdW
>repulsion is the issue here. A normal hydroxyl H does not need a LJ center,
>because it is sufficiently protected by both the O-LJ volume plus, and this
>is key, the relatively stiff angle bending in e.g. C-C-O groups, so the H
>is kept away from the heavy atoms three bonds away. In contrast, a
>phosphate has O-P-O angle terms which are softer plus relatively high
>charges on both H and O, so the collapse you describe between atoms 1 and 4
>in a O-P-O-H substructure can occur. The ad hoc solution of giving the H
>non-zero vdW parameters will make the simulation stable (most likely) but
>in principle you'd be on the hook to show that this still describes the
>phosphate group well in the environment you simulate it in. The cowardly
>solution would be to claim that the phosphate has pK around 7 anyway and in
>the presence of all those nucleic acid associated metal cations, you may as
>well simulate it deprotonated.
Thomas' post seems spot-on to me. One other thing that I remember doing is
to increase the force constant for the P-O-H angle in the monophosphate:
this will help keep the proton from finding a neighboring hydrogen. I'd
double the force constant -- having a slightly-too-stiff angle is not really
going to do anything bad to your sampling.
Let us know if either of both of these ideas (non-zero LJ [try the value for
hydrogens bonded to nitrogen] or stiffer angle) help. We should update the
parameters so that others don't see the problems you are having.
...thanks for the detailed reports....dac
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Received on Wed Mar 22 2023 - 08:30:04 PDT
