Biomedical Engineering Reference
In-Depth Information
should take on faceted forms, as is observed in Fig.
7
. Additionally, we calculated a
reduction in (
30 k
B
T mature) between the states. This
reduction in is functionally important, as it allows the faceted state, with the
high curvature corners, to be adopted at a lower energy cost. Furthermore, it can
be concluded from this analysis that the interactions which are changing during
the transitions, function to reduce making the shell more flexible and enable it
to reach the infectious state more efficiently. From this analysis we have inferred
a mechanical mechanism for the maturation of HK97 by incorporating molecular
details and have provided support for the LMN theory of buckling transitions.
Further examination of larger (T>7) capsid structures using this multiscale
method will allow us to test our predictions from the canonical capsid model that
only
class 2
capsids have the propensity to undergo buckling transitions.
70 k
B
T immature,
6
Conclusions and Future Directions
We have studied several aspects of a virus capsid's behavior ranging from elastic
properties to evolutionary pressures using a variety of modeling techniques. These
techniques span the range from all-atom molecular simulations, to coarse-grained
studies of assembly, to purely mathematical models. Clearly, maturation and capsid
assembly, which are fundamental processes of virus life cycles span a wide range of
spatial and temporal scales. To make progress, we have explored one virus life cycle
process at a time, which allowed us to build models appropriate for the phenomena
under investigation. Even within these independent studies, we have used multiscale
approaches to bridge molecular level detail to continuum theory (Sect.
5
), and
incorporate what we learn at one level of description (
subunit shape
, Sect.
3
), into
our studies of other aspects of the life cycle (
assembly
, Sect.
4
). The current work has
offered explanations for several features of viruses not currently accessible through
experimentation. The goal of all of these works is to gain a better understanding of
how viruses operate and it is this knowledge that will further our ability to fight viral
infections, develop and manufacture vaccines, and utilize capsids in nanotechnology
applications. However, to have an greater impact on health and technology we must
continue our exploration to elucidate the intricate and complex processes of virus
life cycles.
In future studies, we will explore the transition pathways associated with
structural changes of capsids. In an earlier study, normal mode analysis identified
the dominant modes characterizing structural transitions of virus capsids, including
HK97 [
96
]. In the case of HK97, two modes were required to describe the
configurational change. Using these dominant icosahedral normal modes, pathways
were constructed to connect the states of the system. However, these pathways may
not be representative of the physical pathway the virus undergoes, because they are
not refined against an “accurate” potential function. Computing the energetics of
the pathway (free energy barriers, G between stable states) requires using a more
detailed potential. These calculations will require advanced sampling techniques to
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