arXiv subjects

Changbong Hyeon

Publications and source records attributed to Changbong Hyeon.

77 records · Page 5Linked to original sources

arXiv2006

Size, shape, and flexibility of RNA structures

Determination of sizes and flexibilities of RNA molecules is important in understanding the nature of packing in folded structures and in elucidating interactions between RNA and DNA or proteins. Using the coordinates of the structures of RNA in the Protein Data Bank we find that the size of the folded RNA structures, measured using the radius of gyration, $R_G$, follows the Flory scaling law, namely, $R_G =5.5 N^{1/3}$ Åwhere N is the number of nucleotides. The shape of RNA molecules is characterized by the asphericity $Δ$ and the shape $S$ parameters that are computed using the eigenvalues of the moment of inertia tensor. From the distribution of $Δ$, we find that a large fraction of folded RNA structures are aspherical and the distribution of $S$ values shows that RNA molecules are prolate ($S>0$). The flexibility of folded structures is characterized by the persistence length $l_p$. By fitting the distance distribution function $P(r)$ to the worm-like chain model we extracted the persistence length $l_p$. We find that $l_p\approx 1.5 N^{0.33}$ Å. The dependence of $l_p$ on $N$ implies the average length of helices should increases as the size of RNA grows. We also analyze packing in the structures of ribosomes (30S, 50S, and 70S) in terms of $R_G$, $Δ$, $S$, and $l_p$. The 70S and the 50S subunits are more spherical compared to most RNA molecules. The globularity in 50S is due to the presence of an unusually large number (compared to 30S subunit) of small helices that are stitched together by bulges and loops. Comparison of the shapes of the intact 70S ribosome and the constituent particles suggests that folding of the individual molecules might occur prior to assembly.

q-bio.BM↗

arXiv2006

Mechanical unfolding of RNA: From hairpins to structures with internal multiloops

Mechanical unfolding of RNA structures, ranging from hairpins to ribozymes, using laser optical tweezer (LOT) experiments have begun to reveal the features of the energy landscape that cannot be easily explored using conventional experiments. Upon application of constant force ($f$), RNA hairpins undergo cooperative transitions from folded to unfolded states whereas subdomains of ribozymes unravel one at a time. Here, we use a self-organized polymer (SOP) model and Brownian dynamics simulations to probe mechanical unfolding at constant force and constant-loading rate of four RNA structures of varying complexity. Our work shows (i) the response of RNA to force is largely determined by the native structure; (ii) only by probing mechanical unfolding over a wide range of forces can the underlying energy landscape be fully explored.

q-bio.BM↗

arXiv2006

Forced-unfolding and force-quench refolding of RNA hairpins

Using coarse-grained model we have explored forced-unfolding of RNA hairpin as a function of $f_S$ and the loading rate ($r_f$). The simulations and theoretical analysis have been done without and with the handles that are explicitly modeled by semiflexible polymer chains. The mechanisms and time scales for denaturation by temperature jump and mechanical unfolding are vastly different. The directed perturbation of the native state by $f_S$ results in a sequential unfolding of the hairpin starting from their ends whereas thermal denaturation occurs stochastically. From the dependence of the unfolding rates on $r_f$ and $f_S$ we show that the position of the unfolding transition state (TS) is not a constant but moves dramatically as either $r_f$ or $f_S$ is changed. The TS movements are interpreted by adopting the Hammond postulate for forced-unfolding. Forced-unfolding simulations of RNA, with handles attached to the two ends, show that the value of the unfolding force increases (especially at high pulling speeds) as the length of the handles increases. The pathways for refolding of RNA from stretched initial conformation, upon quenching $f_S$ to the quench force $f_Q$, are highly heterogeneous. The refolding times, upon force quench, are at least an order of magnitude greater than those obtained by temperature quench. The long $f_Q$-dependent refolding times starting from fully stretched states are analyzed using a model that accounts for the microscopic steps in the rate limiting step which involves the trans to gauche transitions of the dihedral angles in the GAAA tetraloop. The simulations with explicit molecular model for the handles show that the dynamics of force-quench refolding is strongly dependent on the interplay of their contour length and the persistence length, and the RNA persistence length.

q-bio.BM↗

arXiv2006

Kinetics of Interior Loop Formation in Semiflexible Chains

Loop formation between monomers in the interior of semiflexible chains describes elementary events in biomolecular folding and DNA bending. We calculate analytically the interior distance distribution function for semiflexible chains using a mean-field approach. Using the potential of mean force derived from the distance distribution function we present a simple expression for the kinetics of interior looping by adopting Kramers theory. For the parameters, that are appropriate for DNA, the theoretical predictions in comparison to the case are in excellent agreement with explicit Brownian dynamics simulations of worm-like chain (WLC) model. The interior looping times ($τ_{IC}$) can be greatly altered in cases when the stiffness of the loop differs from that of the dangling ends. If the dangling end is stiffer than the loop then $τ_{IC}$ increases for the case of the WLC with uniform persistence length. In contrast, attachment of flexible dangling ends enhances rate of interior loop formation. The theory also shows that if the monomers are charged and interact via screened Coulomb potential then both the cyclization ($τ_c$) and interior looping ($τ_{IC}$) times greatly increase at low ionic concentration. Because both $τ_c$ and $τ_{IC}$ are determined essentially by the effective persistence length ($l_p^{(R)}$) we computed $l_p^{(R)}$ by varying the range of the repulsive interaction between the monomers. For short range interactions $l_p^{(R)}$ nearly coincides with the bare persistence length which is determined largely by the backbone chain connectivity. This finding rationalizes the efficacy of describing a number of experimental observations (response of biopolymers to force and cyclization kinetics) in biomolecules using WLC model with an effective persistence length.

cond-mat.soft↗

arXiv2005

Mechanical unfolding of RNA hairpins

Mechanical unfolding trajectories, generated by applying constant force in optical tweezer experiments, show that RNA hairpins and the P5abc subdomain of the group I intron unfold reversibly. We use coarse-grained Go-like models for RNA hairpins to explore forced-unfolding over a broad range of temperatures. A number of predictions that are amenable to experimental tests are made. At the critical force the hairpin jumps between folded and unfolded conformations without populating any discernible intermediates. The phase diagram in the force-temperature (f,T) plane shows that the hairpin unfolds by an all-or-none process. The cooperativity of the unfolding transition increases dramatically at low temperatures. Free energy of stability, obtained from time averages of mechanical unfolding trajectories, coincide with ensemble averages which establishes ergodicity. The hopping time between the the native basin of attraction (NBA) and the unfolded basin increases dramatically along the phase boundary. Thermal unfolding is stochastic whereas mechanical unfolding occurs in "quantized steps" with great variations in the step lengths. Refolding times, upon force quench, from stretched states to the NBA is "at least an order of magnitude" greater than folding times by temperature quench. Upon force quench from stretched states the NBA is reached in at least three stages. In the initial stages the mean end-to-end distance decreases nearly continuously and only in the last stage there is a sudden transition to the NBA. Because of the generality of the results we propose that similar behavior should be observed in force quench refolding of proteins.

q-bio.BM↗