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2013 ; 5
(2
): 109-119
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Computer Simulations of the Bacterial Cytoplasm
#MMPMID23914257
Frembgen-Kesner T
; Elcock AH
Biophys Rev
2013[Jun]; 5
(2
): 109-119
PMID23914257
show ga
Ever since the pioneering work of Minton, it has been recognized that the highly
crowded interior of biological cells has the potential to cause dramatic changes
to both the kinetics and thermodynamics of protein folding and association events
relative to behavior that might be observed in dilute solution conditions. One
very productive way to explore the effects of crowding on protein behavior has
been to use macromolecular crowding agents that exclude volume without otherwise
strongly interacting with the protein under study. An alternative, complementary
approach to understanding the potential differences between behavior in vivo and
in vitro is to develop simulation models that explicitly attempt to model
intracellular environments at the molecular scale, and that thereby can be used
to directly monitor biophysical behavior in conditions that accurately mimic
those encountered in vivo. It is with studies of this type that the present
review will be concerned. We review in detail four published studies that have
attempted to simulate the structure and dynamics of the bacterial cytoplasm and
that have each explored different biophysical aspects of the cellular interior.
While each of these studies has yielded important new insights, there are
important questions that remain to be resolved in terms of determining the
relative contributions made by energetic and hydrodynamic interactions to the
diffusive behavior of macromolecules and to the thermodynamics of protein folding
and associations in vivo. Some possible new directions for future generation
simulation models of the cytoplasm are outlined.