Subject: molecular modelling of guanidinium/carboylate interaction

From: [email-masked] (Lutz Ackermann)
Date: Tue, 25 Jan 94 16:02:39 +0100

Dear Netters!

A biochemist, who uses Insight/Discover and Macromodel came along
with an interesting question concerning molecular modelling. I pass
it on to the net, hoping to find experts in this field. Here is
the problem:

The interaction of a guanidinium function and a carboxylate fnc
was modelled using the software cited above (I do not know, which
force fields they used).

                N---H - - - O
               /             \
              /               \ 
     R---N---C +           -   C---R
              \               /
               \             /
                N---H - - - O

In either case they did not obtain a planar geometry. Indeed, the
COO turns out to be almost perpendicular to the C(NH)2 plane, which
is not, what one would intuitively assume to be realistic. So what
might have gone wrong? They don't have any idea, and I (as a new-
comer to the field of MM) only have some vague assumptions. If
you have any experience with such systems, please contact me!
Thank you!

   L. Ackermann

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---

From: Tudor Oprea <[email-masked]>
Date: Tue, 25 Jan 1994 12:58:35 -0600 (CST)

>                           * e-mail   [email-masked]   *

I have tried to model this using the following molecules:
CH3CH2CH2NHC(NH2)2 +1
CH3CH2CH2COO       -1
I used the docking procedure from Cosmic, which centers the target molecule
inside a sphere of 10 A radius (this case), and from uniformly spaced points
(204 in total) sends the mobile molecule towards the center. The 'bullet' is
initially oriented by simplex (rotations @ 60 degrees in all 3 axes), and the
optimal orientation is simplexed towards the target. Butanoic acid was used
as mobile molecule.

The results favor slightly the perpendicular geometry, as shown with Insight &
Macromodel. In this case, four hydrogen bonds are formed (each carboxyl oxygen
is allowed to interact at less than 2.3 A with the two hydrogens depicted in the
figure above). However, 1scf for the perpendicular and the planar geometries
favors the planar one (using VAMP, the AM1 hamiltonian, and 0 formal charge on
a closed shell system). I did not investigate further with QM.

Statistics are given below (energies in kcal/mol, dist in A): 

	   E(Cosmic)  E(AM1)   dCg-Cc  Hbonds # & dist  NC--CO angle
perpend    -32.22     -79.11   3.51    4: 2.03, 1.94    78.3
					  1.85, 2.25
planar     -31.60     -82.09   4.12    2: 1.88, 1.92    3.4

Tudor

                                                     ==========================
  Tudor-Ionel Oprea                                  = Tel. (1-314) 935 4672  =
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