77 research outputs found
Compressive Hyperspectral Imaging Using Progressive Total Variation
Compressed Sensing (CS) is suitable for remote acquisition of hyperspectral
images for earth observation, since it could exploit the strong spatial and
spectral correlations, llowing to simplify the architecture of the onboard
sensors. Solutions proposed so far tend to decouple spatial and spectral
dimensions to reduce the complexity of the reconstruction, not taking into
account that onboard sensors progressively acquire spectral rows rather than
acquiring spectral channels. For this reason, we propose a novel progressive CS
architecture based on separate sensing of spectral rows and joint
reconstruction employing Total Variation. Experimental results run on raw
AVIRIS and AIRS images confirm the validity of the proposed system.Comment: To be published on ICASSP 2014 proceeding
Lipid tempering simulation of model biological membranes on parallel platforms
International audienc
Quantifying the role of chaperones in protein translocation by computational modelling
The molecular chaperone Hsp70 plays a central role in the import of
cytoplasmic proteins into organelles, driving their translocation by binding
them from the organellar interior. Starting from the experimentally-determined
structure of the \textit{E. coli} Hsp70, we computed, by means of molecular
simulations, the effective free-energy profile for substrate translocation upon
chaperone binding. We then used the resulting free energy to quantitatively
characterize the kinetics of the import process, whose comparison with
unassisted translocation highlights the essential role played by Hsp70 in
importing cytoplasmic proteins.Comment: 8 pages, 4 figure
Well-Tempered Metadynamics: A Smoothly Converging and Tunable Free-Energy Method
We present a method for determining the free energy dependence on a selected
number of collective variables using an adaptive bias. The formalism provides a
unified description which has metadynamics and canonical sampling as limiting
cases. Convergence and errors can be rigorously and easily controlled. The
parameters of the simulation can be tuned so as to focus the computational
effort only on the physically relevant regions of the order parameter space.
The algorithm is tested on the reconstruction of alanine dipeptide free energy
landscape
Nucleation of Biomolecular Condensates from Finite-Sized Simulations
The nucleation of protein condensates is a concentration-driven process of assembly. When modeled in the canonical ensemble, condensation is affected by finite-size effects. Here, we present a general and efficient route for obtaining ensemble properties of protein condensates in the macroscopic limit from finite-sized nucleation simulations. The approach is based on a theoretical description of droplet nucleation in the canonical ensemble and enables estimation of thermodynamic and kinetic parameters, such as the macroscopic equilibrium density of the dilute protein phase, the surface tension of the condensates, and nucleation free energy barriers. We apply the method to coarse-grained simulations of NDDX4 and FUS-LC, two phase-separating disordered proteins with different physicochemical characteristics. Our results show that NDDX4 condensate droplets, characterized by lower surface tension, higher solubility, and faster monomer exchange dynamics compared to those of FUS-LC, form with negligible nucleation barriers. In contrast, FUS-LC condensates form via an activated process over a wide range of concentrations
Efficient conversion of chemical energy into mechanical work by Hsp70 chaperones
Hsp70 molecular chaperones are abundant ATP-dependent nanomachines that
actively reshape non-native, misfolded proteins and assist a wide variety of
essential cellular processes. Here we combine complementary
computational/theoretical approaches to elucidate the structural and
thermodynamic details of the chaperone-induced expansion of a substrate
protein, with a particular emphasis on the critical role played by ATP
hydrolysis. We first determine the conformational free-energy cost of the
substrate expansion due to the binding of multiple chaperones using
coarse-grained molecular simulations. We then exploit this result to implement
a non-equilibrium rate model which estimates the degree of expansion as a
function of the free energy provided by ATP hydrolysis. Our results are in
quantitative agreement with recent single-molecule FRET experiments and
highlight the stark non-equilibrium nature of the process, showing that Hsp70s
are optimized to convert effectively chemical energy into mechanical work close
to physiological conditions
Molecular chaperones inject energy from ATP hydrolysis into the non-equilibrium stabilisation of native proteins
Protein homeostasis, namely the ensemble of cellular mechanisms collectively controlling the activity, stability and conformational states of proteins, depends on energy-consuming processes. De novo protein synthesis requires ATP hydrolysis for peptide bond formation. Controlled degradation by the chaperone-gated proteases requires ATP hydrolysis to unfold target proteins and render their peptide bonds accessible to hydrolysis. During and following translation, different classes of molecular chaperones require ATP hydrolysis to control the conformational state of proteins, favor their folding into their active conformation and avoid, under stress, their conversion into potentially harmful aggregates. Furthermore, specific ATP-fueled unfolding chaperones can dynamically revert aggregation itself. We used here various biochemical assays and physical modeling to show that both bacterial chaperones GroEL (HSP60) and DnaK (HSP70) can use the energy liberated by ATP hydrolysis to maintain proteins in their active state even under conditions that do not favor, thermodynamically, the native state. The energy from ATP hydrolysis is thus injected by the chaperones in the system and converted into an enhanced, non-equilibrium steady-state stabilization of the native state of their substrates. Upon ATP consumption, the chaperone substrates spontaneously revert to their equilibrium non-native state
Chaperones convert the energy from ATP into the nonequilibrium stabilization of native proteins.
During and after protein translation, molecular chaperones require ATP hydrolysis to favor the native folding of their substrates and, under stress, to avoid aggregation and revert misfolding. Why do some chaperones need ATP, and what are the consequences of the energy contributed by the ATPase cycle? Here, we used biochemical assays and physical modeling to show that the bacterial chaperones GroEL (Hsp60) and DnaK (Hsp70) both use part of the energy from ATP hydrolysis to restore the native state of their substrates, even under denaturing conditions in which the native state is thermodynamically unstable. Consistently with thermodynamics, upon exhaustion of ATP, the metastable native chaperone products spontaneously revert to their equilibrium non-native states. In the presence of ATPase chaperones, some proteins may thus behave as open ATP-driven, nonequilibrium systems whose fate is only partially determined by equilibrium thermodynamics
Multiple Routes and Milestones in the Folding of HIV–1 Protease Monomer
Proteins fold on a time scale incompatible with a mechanism of random search in conformational space thus indicating that somehow they are guided to the native state through a funneled energetic landscape. At the same time the heterogeneous kinetics suggests the existence of several different folding routes. Here we propose a scenario for the folding mechanism of the monomer of HIV–1 protease in which multiple pathways and milestone events coexist. A variety of computational approaches supports this picture. These include very long all-atom molecular dynamics simulations in explicit solvent, an analysis of the network of clusters found in multiple high-temperature unfolding simulations and a complete characterization of free-energy surfaces carried out using a structure-based potential at atomistic resolution and a combination of metadynamics and parallel tempering. Our results confirm that the monomer in solution is stable toward unfolding and show that at least two unfolding pathways exist. In our scenario, the formation of a hydrophobic core is a milestone in the folding process which must occur along all the routes that lead this protein towards its native state. Furthermore, the ensemble of folding pathways proposed here substantiates a rational drug design strategy based on inhibiting the folding of HIV–1 protease
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