On Thu, Feb 21, 2019 at 9:11 PM Cruzeiro,Vinicius Wilian D <
vwcruzeiro.ufl.edu> wrote:
> The reference energies can also be obtained by performing TI calculations.
>
A word of warning here: TI calculations will always underestimate the
reference energy of protonated species for residues with multiple
protomers. For instance, carboxylate residues have, broadly speaking, 4
different protonation states possible -- they can be in the syn- or anti-
position of either carboxylate oxygen. These are two sets of degenerate
states, with the anti- positions being higher energy than the syn-
positions (but the two anti- and two syn- positions are degenerate with
each other). So Amber defines 5 different states for carboxylate residues
(deprotonated, syn-O1, anti-O1, syn-O2, anti-O2).
By contrast, residues like Tyrosine that have only a single protonable site
(or histidine if you treat each site independently) should have TI energies
that basically exactly match the reference energies (before correcting for
the pKa offset).
As a result, you need to increase the energy gap between the deprotonated
and protonated states in order to compensate for the fact that MC attempts
on protonated states are 4x more likely to happen than MC attempts on the
deprotonated state.
Mongan gives a good description of this in his original 2004 paper
introducing the method.
Good luck,
Jason
--
Jason M. Swails
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Received on Wed Feb 27 2019 - 22:30:04 PST
