Dear Dean,
> In my humble opinion, the most important consideration for correct charge
> derivation is that the conformation of (especially) flexible molecules is
> forced to be as extended as possible to prevent any intramolecular
> interactions (H-bonding) that would corrupt the charge fitting method (the
> documentation to Openeye¹s Quacpak clearly quotes Bayly in this
> regard...).
Kollman's group has clearly defined how should be carried out charge
derivation (1993-1995):
- conformation(s) of molecules involved in charge derivation well
defined - avoid intra-molecular interaction as you said - try using a
conformation close to the experiment; extended conformation? why not,
but not always...
- chemical equivalencing should be carefully done (this is clearly
written in the original paper of Bayly in 1993)
- use of the charge constraints during the fitting step should be
correctly applied
- etc...
> The simplest way to achieve this is use a program like VegaZZ
> to assign charges using their SP4 FF then simply change the signs to be
> all positive or all negative. Then use the SP4 FF to minimize the
> structure. Since all atoms will repel each other, you will (always?)
> achieve the most extended conformation.
Is there a simple way to apply charge derivation for a new biopolymer?
Well I do not think so... Our approach with R.E.D. and R.E.D. Server
is to rigorously apply the approach listed above. So the problem here
is that charge derivation remains a complex task even if we little by
little we automatize it.
See for instance:
http://q4md-forcefieldtools.org/Tutorial/Tutorial-3.php#25
vs
http://q4md-forcefieldtools.org/Tutorial/Tutorial-3.php#24
> Then use MOPAC with AM1 to
> minimize that structure, and then send it to antechamber. My gut feeling
> is that the inconsistent use of the most extended conformations is much
> more detrimental to accurate charge derivations than any advantage sqm
> might have over MOPAC for assigning the AM1BCC charge.
In the original approach Gaussian was used and then GAMESS...
With the RBRA approach implemented in R.E.D. I in 2004
See
http://oasys2.confex.com/acs/227nm/techprogram/P705829.HTM charge
values are reproducible at 1.10-4 e.
> Without knowing if your structure is highly flexible, it's hard to know if
> what I discussed is relevant to your particular situation or not.
Yes!
> At the end of the Ambertools 1.5 it states that for AM1-BCC charges for
> 585 drug molecules, MOPAC and sqm give essentially similar charges for all
> the cases and the average charge difference is 0.005. So what are the
> advantages to sqm over MOPAC for AM1-BCC, since there appears to be tight
> convergence issues with sqm?
Considering that we have no information about the conformation
involved, considering that chemical equivalencing is not correctly
applied, considering that divcon, mopac and sqm were successively
used, considering that convergence criteria were different (see my
next email), "the average charge difference is 0.005" seems unlikely
to me...
regards, Francois
_______________________________________________
AMBER mailing list
AMBER.ambermd.org
http://lists.ambermd.org/mailman/listinfo/amber
Received on Sun Jan 15 2012 - 02:30:02 PST
