Ching-Hsing Yu, Lothar Schäfer, and
Michael Ramek,
Local Geometry Trends and Torsional Sensitivity in
N-Formyl-L-alanyl-L-alanine Amide
and the Limitations of the Dipeptide Approximation
J. Phys. Chem. A, 103, 8337-8345 (1999).
Publication abstract:
Based on a database of 11 664 RHF/4-21G ab initio
gradient-optimized
structures of N-formyl-L-alanyl-L-alanine amide (ALA-ALA), the
local geometries and torsional sensitivity of this compound were
analyzed to test the dipeptide approximation frequently used in peptide
conformational analyses. This database was generated by optimizing the
geometries of this compound at grid points in its four-dimensional
(_{},
_{},
_{},
_{}) conformational
space defined by 40° increments for the outer torsions
_{} and
_{} and by 30° increments
along the inner torsions
_{} and
_{}.
Using cubic spline functions, the grid structures were then used to
construct analytical representations of complete surfaces of the
structural parameters of ALA-ALA, and of their gradients, in
(_{},
_{},
_{},
_{}) space.
Analysis of the structural surfaces shows not only that the structure
of a given residue in a peptide chain depends acutely on the conformational
state of a neighboring residue but also that the interresidue effects
differ, depending on whether they are transmitted from right to left or
from left to right in the peptide chain.
Structural gradients are a qualitative measure of the torsional sensitivity,
and therefore of the density of states and contributions
to vibrational entropy. Analyses of the gradient surfaces show that the
density of states in a residue is significantly affected by the dynamics
of a neighboring residue. This opens the possibility of dynamic entropic
conformational steering in extended peptide chains, i.e.,
the generation of free energy contributions from dynamic effects of
one part of a molecule on another, possibly stabilizing a conformational
region of a potential energy surface whose static energy profile is less
favorable compared to other regions. The gradient trands illustrate how
the overall stability of a complex molecule is not only a function of
how the static energy minima of its isolated subunits combine but also of how
the dynamics of the subunits interact with one other. These interactions
between individual residues represent a hidden cooperative effect that
is not apparent at all in the dynamics of isolated dipeptide units.