Biomedical Engineering Reference
In-Depth Information
the simulation studies of T
D
1; 3; 4; 7; 9; 12; 13; 16; and 19 systems, we observed
the formation of a variety of nonicosahedral yet highly ordered and enclosed
capsules in addition to the expected icosahedral capsids. These simulations demon-
strate that structural polymorphism is independent of the capsid complexity and
the elementary kinetic mechanisms of self-assembly. Furthermore, the simulations
revealed the existence of two distinctive and comprehensive classes of polymorphic
structures. The first class includes aberrant capsules that are larger than their
respective icosahedral capsids in T
D
1
7 systems and the second class includes
capsules that are smaller than their respective icosahedral capsids in T
D
7
19
systems (Fig.
6
b). The kinetic mechanisms responsible for the self-assembly of
these two classes of aberrant structures were deciphered, providing insights into how
to control the self-assembly of icosahedral capsids. To our knowledge, this is one
of the first simulation studies that provided a generalized description of structural
polymorphism, which is often observed in
in vitro
experiments [
14
,
68
-
70
,
72
,
73
]
and vaccine development studies [
71
].
Simulation studies, as described here, can provide new tools to inform potential
strategies in antiviral development, protein design, and the engineering of novel
biomaterials. The methodology employed in these studies could also be expanded
upon to elucidate the means by which capsid proteins and the viral genome are
self-assembled into full viruses. Such studies would enable us to make unique
contributions to the field of virology/medicine by suggesting the development of
novel ways to interfere with virus assembly and ultimately with viral infections.
5
Maturation and Mechanical Properties of Virus Capsids
An important aspect of designing nanotechnologies is material characterization;
understanding how the material responds to stresses and different environmental
conditions and ultimately the calculation of the fundamental mechanical moduli.
Characterization of the mechanical properties of virus capsids is important for
technology design as well as understanding the maturation phenomenon, which is
one of the most fundamental process of the virus life cycle.
The T
D
7 bacteriophage HK97 is a widely studied system [
13
,
76
-
81
], due to
its interesting structural features. This virus assembles into a procapsid structure
consisting of 420 copies of a single protein and initially forms a rounded procapsid
structure (Prohead II) as shown in Fig.
7
on the left. The seven protein asymmetric
unit of Prohead II is also shown in Fig.
8
.
In vivo
the structure matures upon pack-
aging of the DNA genome, during which the structure expands, becomes faceted,
and iso-peptide bonds form between side chains of different proteins, resulting in
the mature (Head II) structure as shown in Fig.
7
on the right. The maturation
transition (commonly termed a buckling transition) can also be triggered
in vitro
with empty capsids (genome deficient), by lowering the system pH [
77
,
82
]. This
maturation-related structural transition has broad implications for understanding
virus behavior [
83
]. HK97 is believed to share many aspects of its maturation
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