First-Principles-Based Multiscale, Multiparadigm Molecular Mechanics and Dynamics Methods for Describing Complex Chemical Processes - Multiscale Molecular Methods in Applied Chemistry - page 33

Fig. 17 Comparison of average MD structures between meso-scale and atomistic

observed in the case of the atomistic DNA, contrasted with the irregular profile for
the meso-scale case. The overlay of the two structures illustrated the sharp differ-
ences in the backbone torsions of the atomistic (blue) and the meso scale (red)
structures. A considerably larger distortion can be seen for the meso structure, in
particular the presence of several backbone kinks. The backbone parameters for
both sets of simulation are within the acceptable range of B-DNA, except for
the backbone twist, where the average MD structures are under-twisted (this is
a known issue with the AMBER force field). There is also significant deviation in
the backbone twist for the meso dodecamer, which is a consequence of the
aforementioned kinks in the structure.
From these helical analyses it is clear that further optimization of the meso-scale
force field is required. In particular, the Phosphate-Sugar-Phosphate backbone twist
angle and the Phosphate-Sugar-Phosphate-Sugar backbone dihedral angles need to
be optimized to prevent the under-twisting of the helix seen in the dodecamer
simulation. The helical rise in the meso-scale dodecamer is outside the accepted
range for B-DNA (3.4

0.2) which, when combined with the under-twisting of the
helix, points to unwinding of the helix.
The following section describes the application of QM-parameterized atomistic
and coarse-grain potentials to tissue engineering.

4.1.2 Application Example: Mechanoregulation in Polymer-Based
Hydrogel Networks for Tissue Engineering

We are currently studying the nanoscale properties that lead to improved micro-
scale mechanoregulatory response of polymer-based hydrogel networks for carti-
lage tissue scaffolding. The structural similarity of synthetic polymer-based hydrogels
to the collagen ECM found in human cartilage and their ease of processability
makes them ideal candidates for cartilage scaffold-supported cell therapies [ 131 ].
These hydrogels can act as a temporary artificial extra cellular matrix (ECM) to
provide mechanical support, or provide the ambience for new cells to grow towards