An investigation has
been performed to assess how aqueous dynamical simulations of flexi
blemolecules can
be compared against NMR data. The methodology compares state-of-the-art NMR data (residualdipolar coupling, NOESY, and
13C relaxation) to molecular dynamics simulations in water over severalnanoseconds. In contrast to many previous applications of residual dipolar coupling in structure investigationsof
biomolecules, the approach descri
bed here uses molecular dynamics simulations to provide a dynamicrepresentation of the molecule. A mannose pentasaccharide,
![](/images/gifchars/alpha.gif)
-
D-Man
p-(1
![](/images/entities/rarr.gif)
3)-
![](/images/gifchars/alpha.gif)
-
D-Man
p-(1
![](/images/entities/rarr.gif)
3)-
![](/images/gifchars/alpha.gif)
-
D-Man
p-(1
![](/images/entities/rarr.gif)
3)-
![](/images/gifchars/alpha.gif)
-
D-Man
p-(1
![](/images/entities/rarr.gif)
2)-
D-Man
p, was chosen as the model compound for this study. The presence of
![](/images/gifchars/alpha.gif)
-linkedmannan is common to many glycopeptides, and therefore an understanding of the structure and the dynamicsof this molecule is of
both chemical and
biological importance. This paper sets out to address the followingquestions. (1) Are the single structures which have
been used to interpret residual dipolar couplings a usefulrepresentation of this molecule? (2) If dynamic flexi
bility is included in a representation of the molecule, canrelaxation and residual dipolar coupling data then
be simultaneously satisfied? (3) Do aqueous moleculardynamics simulations provide a reasona
ble representation of the dynamics present in the molecule and itsinteraction with water? In summary, two aqueous molecular dynamics simulations, each of 20 ns, were computed.They were started from two distant conformations and
both converged to one flexi
ble ensem
ble. The measuredresidual dipolar couplings were in agreement with predictions made
by averaging the whole ensem
ble andfrom a specific single structure selected from the ensem
ble. However, the inclusion of internal motion wasnecessary to rationalize the relaxation data. Therefore, it is proposed that although residual dipolar couplingscan
be interpreted as a single-structure, this may not
be a correct interpretation of molecular conformation inlight of other experimental data. Second, the methodology descri
bed here shows that the ensem
bles fromaqueous molecular dynamics can
be effectively tested against experimental data sets. In the simulation, significantconformational motion was o
bserved at each of the linkages, and no evidence for intramolecular hydrogen
bonds at either
![](/images/gifchars/alpha.gif)
(1
![](/images/entities/rarr.gif)
2) or
![](/images/gifchars/alpha.gif)
(1
![](/images/entities/rarr.gif)
3) linkages was found. This is in contrast to simulations of other linkages,such as
![](/images/gifchars/<font color=)
beta2.gif" BORDER=0 ALIGN="middle">(1
![](/images/entities/rarr.gif)
4), which are often predicted to maintain intramolecular hydrogen
bonds and are coincidentallypredicted to have less conformational freedom in solution.