Multiscale Modeling of Virus Structure, Assembly, and Dynamics - Computational Modeling of Biological Systems - page 184

“find” a minimal energy pathway and then compute the probabilities of the states
along the path [ 97 - 99 ]. Understanding how pH effects the energetics of the pathway
can also be incorporated into our pathway modeling efforts through constant pH-
MD methods [ 100 , 101 ]. The potential benefit of studying these transition pathways
is that molecular interactions that have a drastic effect on the behavior of the system
can be identified. For example, specific salt bridges might form at a given pH, but
altering the pH could break those salt bridges and change the free energy barrier
between the stable states. Identification of these key residues can be tested through
mutagenesis studies, and could provide a target for preventing virus maturation.
Similarly, the pathway methods can be combined with elasticity calculations such as
described above, and residues that are responsible for altering the elastic character
of the material can be identified. This knowledge could provide design principles
for engineering novel capsids and for modulating the properties of capsids used in
nanotechnologies. Understanding transition pathways is just one avenue of further
investigation of viruses, other areas of interest include understanding viral protein-
host protein interactions [ 102 ] and protein-nucleic acid interactions during virus
assembly. Viruses have a rich array of features and phenomena that are still poorly
understood. However, by building and employing computational and theoretical
models that capture the essential physics of the underlying phenomenon, we can
shed light on many of these unresolved aspects of the virus life cycle.
Acknowledgments This work has been supported by the NSF through the center for theoretical
biological physics (CTBP) at the University of California, San Diego (PHY0216576), by the
National Institute of Health for funding through the multiscale modeling tools for structural biology
(MMTSB) research resource center RR012255, and research grant GM037555, and by the National
Science Foundation through a postdoctoral fellowship to ERM (DBI-0905773).
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