اشترك بالحزمة الذهبية واحصل على وصول غير محدود شمرا أكاديميا
تسجيل مستخدم جديدViscoelasticity of model interphase chromosomes
210
0
0.0
(
0
)
اسأل ChatGPT حول البحث
ﻻ يوجد ملخص باللغة العربية
We investigated the viscoelastic response of model interphase chromosomes by tracking the three-dimensional motion of hundreds of dispersed Brownian particles of sizes ranging from the thickness of the chromatin fiber up to slightly above the mesh size of the chromatin solution. In agreement with previous computational studies on polymer solutions and melts, we found that the large-time behaviour of diffusion coefficient and the experienced viscosity of moving particles as functions of particle size deviate from the traditional Stokes-Einstein relation, and agree with a recent scaling theory of diffusion of non-sticky particles in polymer solutions. Interestingly, we found that at short times large particles are temporary caged by chromatin spatial constraints, which thus form effective domains whose size match remarkably well recent experimental results for micro-tracers inside interphase nuclei. Finally, by employing a known mathematical relation between the time mean-square displacement of tracked particles and the complex shear modulus of the surrounding solution, we calculated the elastic and viscous moduli of interphase chromosomes.
قيم البحث
اقرأ أيضاً
Biophysicists are modeling conformations of interphase chromosomes, often basing the strengths of interactions between segments distant on the genetic map on contact frequencies determined experimentally. Here, instead, we develop a fitting-free, min
imal model: bivalent red and green transcription factors bind to cognate sites in runs of beads (chromatin) to form molecular bridges stabilizing loops. In the absence of additional explicit forces, molecular dynamic simulations reveal that bound factors spontaneously cluster -- red with red, green with green, but rarely red with green -- to give structures reminiscent of transcription factories. Binding of just two transcription factors (or proteins) to active and inactive regions of human chromosomes yields rosettes, topological domains, and contact maps much like those seen experimentally. This emergent bridging-induced attraction proves to be a robust, simple, and generic force able to organize interphase chromosomes at all scales.
A major challenge in molecular simulations is to describe denaturant-dependent folding of proteins order to make direct comparisons with {it in vitro} experiments. We use the molecular transfer model, which is currently the only method that accomplis
hes this goal albeit phenomenologically, to quantitatively describe urea-dependent folding of PDZ domain, which plays a significant role in molecular recognition and signaling. Experiments show that urea-dependent unfolding rates of the PDZ2 domain exhibit a downward curvature at high urea concentrations, which has been interpreted by invoking the presence of a sparsely populated high energy intermediate. Simulations using the MTM and a coarse-grained model of PDZ2 are used to show that the intermediate, which has some native-like character, is present in equilibrium both in the presence and absence of urea. The free energy profiles show that there are two barriers separating the folded and unfolded states. Structures of the transition state ensembles, ($TSE1$ separating the unfolded and $I_{EQ}$ and $TSE2$ separating $I_{EQ}$ and the native state), determined using the $P_{fold}$ method, show that $TSE1$ is expanded; $TSE2$ and native-like. Folding trajectories reveal that PDZ2 folds by parallel routes. In one pathway folding occurs exclusively through $I_1$, which resembles $I_{EQ}$. In a fraction of trajectories, constituting the second pathway, folding occurs through a combination of $I_{1}$ and a kinetic intermediate. The radius of gyration ($R_g^{U}$) of the unfolded state is more compact (by $sim$ 9%) under native conditions. Decrease in $R_g^{U}$ occurs on the time scale on the order of utmost $sim$ 20 $mu s$. The modest decrease in $R_g^{U}$ and the rapid collapse suggest that high spatial and temporal resolution are needed to detect compaction in finite-sized proteins.
We study the behavior of five proteins at the air-water and oil-water interfaces by all-atom molecular dynamics. The proteins are found to get distorted when pinned to the interface. This behavior is consistent with the phenomenological way of introd
ucing the interfaces in a coarse-grained model through a force that depends on the hydropathy indices of the residues. Proteins couple to the oil-water interface stronger than to the air- water one. They diffuse slower at the oil-water interface but do not depin from it, whereas depinning events are observed at the other interface. The reduction of the disulfide bonds slows the diffusion down.
Intrinsically disordered proteins (IDPs) do not possess well-defined three-dimensional structures in solution under physiological conditions. We develop all-atom, united-atom, and coarse-grained Langevin dynamics simulations for the IDP alpha-synucle
in that include geometric, attractive hydrophobic, and screened electrostatic interactions and are calibrated to the inter-residue separations measured in recent smFRET experiments. We find that alpha-synuclein is disordered with conformational statistics that are intermediate between random walk and collapsed globule behavior. An advantage of calibrated molecular simulations over constraint methods is that physical forces act on all residues, not only on residue pairs that are monitored experimentally, and these simulations can be used to study oligomerization and aggregation of multiple alpha-synuclein proteins that may precede amyloid formation.
The molecular motor myosin V exhibits a wide repertoire of pathways during the stepping process, which is intimately connected to its biological function. The best understood of these is hand-over-hand stepping by a swinging lever arm movement toward
the plus-end of actin filaments, essential to its role as a cellular transporter. However, single-molecule experiments have also shown that the motor foot stomps, with one hand detaching and rebinding to the same site, and backsteps under sufficient load. Explaining the complete taxonomy of myosin Vs load-dependent stepping pathways, and the extent to which these are constrained by motor structure and mechanochemistry, are still open questions. Starting from a polymer model, we develop an analytical theory to understand the minimal physical properties that govern motor dynamics. In particular, we solve the first-passage problem of the head reaching the target binding site, investigating the competing effects of load pulling back at the motor, strain in the leading head that biases the diffusion in the direction of the target, and the possibility of preferential binding to the forward site due to the recovery stroke. The theory reproduces a variety of experimental data, including the power stroke and slow diffusive search regimes in the mean trajectory of the detached head, and the force dependence of the forward-to-backward step ratio, run length, and velocity. The analytical approach yields a formula for the stall force, identifying the relative contributions of the chemical cycle rates and mechanical features like the bending rigidities of the lever arms. Most importantly, by fully exploring the design space of the motor, we predict that myosin V is a robust motor whose dynamical behavior is not compromised by reasonable perturbations to the reaction cycle, and changes in the architecture of the lever arm.
سجل دخول لتتمكن من نشر تعليقات
التعليقات
جاري جلب التعليقات
سجل دخول لتتمكن من متابعة معايير البحث التي قمت باختيارها
