Hi all,
Lately I've been doing some small molecule work (including several
side chain analogues) and noticed something odd about the atom types
of the LYN (neutral lysine) side chain. In both AMBER ff9x/ff03 and
GAFF, there are different atom types for:
(1) protons bonded to a sp3 carbon bonded to a positively charged
group (i.e., HP or hx) vs. protons bonded to a sp3 carbon bonded to a
neutral, but electron-withdrawing group (i.e., H1 or h1)
(2) a nitrogen atom in a positively charged amine group (i.e., N3 or
n4) vs. a nitrogen atom in a neutral amine group (i.e., N or n)
And indeed if one uses antechamber to assign atom types to methylamine
and methylammonium, for example, the assigned GAFF atom types are
different. For methylamine, the atom types are c3, n3, h1, and hn;
for methylammonium, the atom types are c3, n4, hx, hn. (The same also
occurs for n-butylamine and n-butylammonium, which are more directly
analogous to the neutral and positively charged lysine side chains,
respectively.)
If one examines all_amino94.lib or all_amino03.lib, however, the atom
types for the last two "groups" (i.e., CE+HE* and NZ+HZ*) of both the
LYN and LYS side chains are CT, HP, N3, and H. In other words, no
distinction is made between the atom types of the neutral vs.
positively charged terminal groups.
If one were to use N (the notionally "correct" atom type) instead of
N3 for LYN, I don't think this would change things much as the vdW
parameters are identical and the bonded parameters are generally very
similar (and quite often identical). If one were to use H1 instead of
HP for LYN, however, I'm not sure that the story would be the same as
the vdW parameters differ significantly, thereby altering solute-
solute and solute-solvent interactions. Admittedly the difference in
net charge is probably far more significant in the resulting behavior
of the neutral vs. charged side chain, but nonetheless it appears that
Veenstra et al. found different optimal solutions for the HP and H1
parameters when examining dimers of water with methylamine vs.
methylammonium.
What I am wondering is how this choice of atom types for the LYN side
chain was rationalized given that there were/are existing alternative
atom types (as demonstrated when using antechamber for small molecule
analogues) or if this was possibly an oversight in defining the
residue way back when.
Best,
Paul
_______________________________________________
AMBER mailing list
AMBER.ambermd.org
http://lists.ambermd.org/mailman/listinfo/amber
Received on Wed Apr 27 2011 - 18:30:02 PDT
