Subject: G: PM3 ESP charges (Summary)

From: [email-masked]
Date: Fri, 10 Dec 1999 16:51:02 +0100

A while ago I posted a question concerning  the calculation of ESP derived
charges in G98;
for the semiempirical AM1 and PM3 calculations, these ESP charges looked
pretty weird.

I have received a couple of responses which I (finally, finally) want to
summarize. 
At the end, Ive added the original query.

- George Ford from the SMU in Dallas was very helpful in first confirming my
G98 results with
  G94 (i.e. getting the same rubbish numbers that I got), and then running
the same input geometry
  in his MOPAC or Spartan copy (mopac93 v.2) and getting reasonable numbers
back. 
- Richard Dixon (BASF) suspected that "
	most semi-empirical ESP charge routines first deorthogonalize the
basis by fitting to
	some sort of gaussian approximation (STO-6G in mopac for example)
The
	electrostatic potential is then calculated with respect to this
basis.  My first
	guess is that you are using the orthogonal PM3 basis for your charge
	calculation.  If so, and if G98 does not have the "correct"
algorithm available,
	you may want to check out some other program."
- Don Boyd pointed me to a chapter by Francl and Chirlian in Vol. 14 of
Reviews in 
  Compuational Chemistry. The chapter supposedly (unfortunately I dont have
this
  issue yet) gives an review of the problem and what can be done to try to
fix it.

Well, bottom line is that if you want ESP derived charges from a
semiempricial
wavefunction, Gaussian is not the method of choice.

Thanks again to all who helped me with this problem.

Th.

--- ORIGINAL QUESTION--
I am investigating some small molecule inhibitors of thrombin (20-30 heavy
atoms) and try to
extract some atomic charges with different methods and at various levels of
theory with G98 Rev A7. While the
Mulliken charges at all levels, and the HF-ESP charges (POP=MK, or
POP=CHELP)  look pretty reasonable,
I have problems with the ESP charges generated by a AM1 or PM3 calculation.
For some atoms I get
charges of the order of +-10 ! 
I do know that the fitting procedure simply tries to reproduce the
electrostatic potential of the wavefunction
as accurately as possible and does not take into account chemical intuition
or my prejudices about how
big partial charges should be, and I also know the discussion of the
underdetermined buried atoms, but still,
'partial' charges of this magnitude seem a little excessive to
me...especially as the same molecules
treated at HF level give atomic charges that very well agree with what I
would have expected.

So...my questions are:
1) has anybody experienced a similar behavior (which would make me much more
confident that I didnt goof
    at some point, or that there is a bug in the new semiempirical routine)
or has it been described before?
2) if my results are correct, can one rationalize why the semiempirical ESP
charges are so different
    from the HF ones? My first guess would be that a 6-31G generated ESP is
'smoother' than a minimal basis
    one from the semiempirical calculations, and therefore easier to fit
with atom centered monopoles, but is
    this really the reason?

-- 

Dr. Thomas Fox
Dept. Chemical Reseach / Structural Research
Boehringer Ingelheim Pharma KG
88397 Biberach/Germany
[email-masked]