Modeling the Peptide Amide Link – N-methylacetamide.
Methodology.
Molecular Mechanics (Force Field)
MNDO/AM1/PM3 (Semiempirical)
Techniques Used.
Building, optimization, bond constraints
Abstract. N-methylacetamide (NMA) provides
a simple model for the structure and conformational characteristics of the
peptide. The strong preference for the trans conformation and the sizeable
barrier to rotation characteristic of the amide bond can be studied using
either adequately-parameterized force field methods or semiempirical methods.
It is worth noting that the NDO-MO semiempirical methods (MNDO, AM1, PM3)
require a special correction for amide computations, which must be enabled
to take effect at present. This exercise is aimed at carrying out a typical
model study for a type of bond in a larger system.
Procedure. Use an appropriate force field that
has good parameterization for amide/peptide type bonds (OPLS, Amber, CHARMm).
Alternatively, use the AM1 or PM3 method as a test of quantum mechanical
methods for this problem.
Build and optimize both the cis and trans forms of NMA, using both a
standard force field such as MM+/MMX/MM2 and a bio-specialized
force field such as OPLS. Compare the energy differences between the cis
and trans forms, and the geometries from the different methods. Experimental
and ab initio computational values for these data are given below. See W.
L. Jorgensen & J. Gao, J. Am. Chem. Soc., 110, 4212 (1988).
If you try to use AM1/PM3 instead of OPLS, you will be able to obtain
information such as bond order and charge distribution (for Hyperchem, this
involves saving a LOG file of the calculation in advance). Note in particular
the bond order of the C-N bond, and the charge distributions.
The bond rotation of a peptide CO-NH bond typically requires about 18-20
kcal/mol. See if you can reproduce this result by carrying out a computation
on a 90 degree twisted form of NMA, using any of the methods you are using
above.
Results.
