1,360 research outputs found
Effects of confinement and crowding on folding of model proteins
We perform molecular dynamics simulations for a simple coarse-grained model
of crambin placed inside of a softly repulsive sphere of radius R. The
confinement makes folding at the optimal temperature slower and affects the
folding scenarios, but both effects are not dramatic. The influence of crowding
on folding are studied by placing several identical proteins within the sphere,
denaturing them, and then by monitoring refolding. If the interactions between
the proteins are dominated by the excluded volume effects, the net folding
times are essentially like for a single protein. An introduction of
inter-proteinic attractive contacts hinders folding when the strength of the
attraction exceeds about a half of the value of the strength of the single
protein contacts. The bigger the strength of the attraction, the more likely is
the occurrence of aggregation and misfolding
Confinement Effects on the Kinetics and Thermodynamics of Protein Dimerization
In the cell, protein complexes form relying on specific interactions between
their monomers. Excluded volume effects due to molecular crowding would lead to
correlations between molecules even without specific interactions. What is the
interplay of these effects in the crowded cellular environment? We study
dimerization of a model homodimer both when the mondimers are free or tethered
to each other. We consider a structured environment: Two monomers first diffuse
into a cavity of size and then fold and bind within the cavity. The folding
and binding are simulated using molecular dynamics based on a simplified
topology based model. The {\it confinement} in the cell is described by an
effective molecular concentration . A two-state coupled folding
and binding behavior is found. We show the maximal rate of dimerization
occurred at an effective molecular concentration M which is a
relevant cellular concentration. In contrast, for tethered chains the rate
keeps at a plateau when .
For both the free and tethered cases, the simulated variation of the rate of
dimerization and thermodynamic stability with effective molecular concentration
agrees well with experimental observations. In addition, a theoretical argument
for the effects of confinement on dimerization is also made
Ion-mediated RNA structural collapse: effect of spatial confinement
RNAs are negatively charged molecules residing in macromolecular crowding
cellular environments. Macromolecular confinement can influence the ion effects
in RNA folding. In this work, using the recently developed tightly bound ion
model for ion fluctuation and correlation, we investigate the confinement
effect on the ion-mediated RNA structural collapse for a simple model system.
We found that, for both Na and Mg, ion efficiencies in mediating
structural collapse/folding are significantly enhanced by the structural
confinement. Such an enhancement in the ion efficiency is attributed to the
decreased electrostatic free energy difference between the compact conformation
ensemble and the (restricted) extended conformation ensemble due to the spatial
restriction.Comment: 22 pages, 5 figure
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Lipid vesicles chaperone an encapsulated RNA aptamer.
The organization of molecules into cells is believed to have been critical for the emergence of living systems. Early protocells likely consisted of RNA functioning inside vesicles made of simple lipids. However, little is known about how encapsulation would affect the activity and folding of RNA. Here we find that confinement of the malachite green RNA aptamer inside fatty acid vesicles increases binding affinity and locally stabilizes the bound conformation of the RNA. The vesicle effectively 'chaperones' the aptamer, consistent with an excluded volume mechanism due to confinement. Protocellular organization thereby leads to a direct benefit for the RNA. Coupled with previously described mechanisms by which encapsulated RNA aids membrane growth, this effect illustrates how the membrane and RNA might cooperate for mutual benefit. Encapsulation could thus increase RNA fitness and the likelihood that functional sequences would emerge during the origin of life
Capturing the essence of folding and functions of biomolecules using Coarse-Grained Models
The distances over which biological molecules and their complexes can
function range from a few nanometres, in the case of folded structures, to
millimetres, for example during chromosome organization. Describing phenomena
that cover such diverse length, and also time scales, requires models that
capture the underlying physics for the particular length scale of interest.
Theoretical ideas, in particular, concepts from polymer physics, have guided
the development of coarse-grained models to study folding of DNA, RNA, and
proteins. More recently, such models and their variants have been applied to
the functions of biological nanomachines. Simulations using coarse-grained
models are now poised to address a wide range of problems in biology.Comment: 37 pages, 8 figure
Hydrophobic and ionic-interactions in bulk and confined water with implications for collapse and folding of proteins
Water and water-mediated interactions determine thermodynamic and kinetics of
protein folding, protein aggregation and self-assembly in confined spaces. To
obtain insights into the role of water in the context of folding problems, we
describe computer simulations of a few related model systems. The dynamics of
collapse of eicosane shows that upon expulsion of water the linear hydrocarbon
chain adopts an ordered helical hairpin structure with 1.5 turns. The structure
of dimer of eicosane molecules has two well ordered helical hairpins that are
stacked perpendicular to each other. As a prelude to studying folding in
confined spaces we used simulations to understand changes in hydrophobic and
ionic interactions in nano droplets. Solvation of hydrophobic and charged
species change drastically in nano water droplets. Hydrophobic species are
localized at the boundary. The tendency of ions to be at the boundary where
water density is low increases as the charge density decreases. Interaction
between hydrophobic, polar, and charged residue are also profoundly altered in
confined spaces. Using the results of computer simulations and accounting for
loss of chain entropy upon confinement we argue and then demonstrate, using
simulations in explicit water, that ordered states of generic amphiphilic
peptide sequences should be stabilized in cylindrical nanopores
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