Subject: G: PM3 ESP charges

From: [email-masked]
Date: Mon, 20 Sep 1999 11:14:46 +0200

Hi everybody -

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?

Thanks a lot,
Th.

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