Computational Approaches in Peptide and Protein Design: An Overview - Peptide and Protein Design for Biopharmaceutical Applications - page 11

inverted g-turn). The lower-right quadrant contains the (80, 80) point
that corresponds to the C 7 ax conformation (the g-turn). At this rough 'quad-
rant' approximation, all quadrants except the lower-right are considered
sterically allowed for the L -amino acid residues. All four quadrants are
allowed for Gly residues but only two of them, namely those at the left side
of the plot, are allowed for L -Pro residues. The Ramachandran maps for L -and
D -amino acid residues are symmetrical with respect to rotation by 180
around an orthogonal axis at the centre of the map.
Earlier calculations of the Ramachandran map for Ac-Ala-OMe using
CHARMM and AMBER, but not those using ECEPP, showed that con-
formation C 7 ax possessed relative energies close to those of C 7 eq ,the
conformation with the lowest energy [24]. Moreover, the CHARMM
and AMBER maps showed fairly large regions of energetically-allowed
conformations in the lower-right quadrant, which was contradictive to
data on the X-ray structures of amino acid residues in proteins available at
the time (1989). It was argued that the calculations were performed with-
out proper account for solvent and, in fact, modelled the Ac-Ala-OMe in
the gas phase, for which no experimental data exists. On the other hand,
high-level quantum calculations for Ac-Ala-OMe also found that confor-
mation C 7 ax possesses energy close to C 7 eq and lower than conformations
corresponding to the right- or left-handed a-helical structures (e.g. [25]).
Recently, the Ramachandran map for Ac-Ala-OMe was extensively
sampled by molecular dynamics simulations employing several force
fields with flexible valence geometry [1]. Simulations included interac-
tions with water molecules described explicitly. Figure 2.1(a) (d) depicts
the Ramachandran maps obtained with the AMBER, CHARM22,
GROMOS and OPLS-AA force fields, respectively. Figure 2.1(e) depicts
the distribution of the (f, c) positions for each of 97 368 residues derived
from 500 high-resolution X-ray structures of proteins [2]; to avoid bias,
only the data for residues not involved in regular secondary structures
such as b-strands or a-helices were included in the map in Figure 2.1(e).
Assuming that the distribution of the X-ray data on residues in proteins is
a good approximation of the general distribution of plausible (f, c)
values for peptides and proteins, one can utilize this distribution to
evaluate the relative validity of various force fields for computational
studies of peptides and proteins.
Experimental data presented in Figure 2.1(e) suggest that most plau-
sible conformations of the L -amino acid residues in proteins are concen-
trated into three regions. The largest and most populated region is located
in the upper-left quadrant of the Ramachandran map, encompassing
conformations corresponding to the b-strand and P II (the 'beta' region).