Ring dihedral Principal Component Analysis of furanose conformation - Carbohydrate Chemistry: Chemical and Biological Approaches - page 394

Fig. 11 RdPCA 3D-free energy representation of the dihydroxylated compound IV; each
of the nine iso-surfaces corresponds to points of the 3D-space (PC1, PC2, PC3) with a
constant free energy isovalue (in kcal.mol 1 ); the ring symbolizes the projection on the
previous (PC1, PC2) 2D-representation; charge set 1 in explicit water (1 ns).
emphasized. This influence was observed earlier, but was not displayed
as clearly on the 1D-free energy profile G = f(P) in Fig. 6.
6 Conclusions and perspectives
Molecular modelling at the DFT level of theory were used to identify
minimum energy conformations of furanose rings and to generate 1-D
energy profiles as a function of the puckering angle P. In addition, full
quantum molecular dynamics (CPMD) studies were performed, in par-
allel with classical molecular dynamics, in order to provide additional
insight and to test the reliability of using constant partial charges in
classical approaches. Conventional Altona-based models describe
furanose conformation in terms of two parameters, P and y m , that may
significantly exclude portions of conformational space. We have de-
veloped here a new representation system we called RdPCA to charac-
terize ring flexibility based on the choice of the most energetically
relevant axes, with none of the assumptions underlying the Altona model.
This new representation may also help in force field development since
the free energy surface is reduced to a function of a few important col-
lective degrees of freedom, which describe the underlying physics of the
sugar ring during the simulation.
Our observations suggest that:
- the conformational behaviour of the tetrahydropyran ring cannot be
described in terms of discrete static conformations, but only in terms of
conformational space, ranging broadly over both P and y m . Within this
model family, it is clear that puckering and y m must both be taken into
account in order to describe the free energy landscape.
- molecular dynamics are necessary to describe conformational space.
The use of constant partial charges in classical dynamics does not have as
significant an impact in a vacuum, as the use of fixed solvent charges in
the case of explicit water. In the latter case, quantum mechanical dy-
namics give a significantly different energy profile, and may be necessary
to reproduce experimentally observed data.