Biology subjects

Changbong Hyeon

Publications and source records attributed to Changbong Hyeon.

3 recordsLinked to original sources

bioRxiv2016

Ripping RNA by Force using Gaussian Network Models

Using force as a probe to map the folding landscapes of RNA molecules has become a reality thanks to major advances in single molecule pulling experiments. Although the unfolding pathways under tension are complicated to predict studies in the context of proteins have shown that topology plays is the major determinant of the unfolding landscapes. By building on this finding we study the responses of RNA molecules to force by adapting Gaussian network model (GNM) that represents RNAs using a bead-spring network with isotropic interactions. Cross-correlation matrices of residue fluctuations, which are analytically calculated using GNM even upon application of mechanical force, show distinct allosteric communication as RNAs rupture. The model is used to calculate the force-extension curves at full thermodynamic equilibrium, and the corresponding unfolding pathways of four RNA molecules subject to a quasi-statically increased force. Our study finds that the analysis using GNM captures qualitatively the unfolding pathway of T. ribozyme elucidated by the optical tweezers measurement. However, the simple model is not sufficient to capture subtle features, such as bifurcation in the unfolding pathways or the ion effects, in the forced-unfolding of RNAs.

Biophysics↗

bioRxiv2016

Ultraslow water-mediated transmembrane interactions regulate the activation of A2A adenosine receptor

Water molecules inside G-protein coupled receptor have recently been spotlighted in a series of crystal structures. To decipher the dynamics and functional roles of internal waters in GPCR activity, we studied A2A adenosine receptor using sec-molecular dynamics simulations. Our study finds that the amount of water flux across the transmembrane (TM) domain varies depending on the receptor state, and that the water molecules of the TM channel in the active state flow three times slower than those in the inactive state. Depending on the location in solvent-protein interface as well as the receptor state, the average residence time of water in each residue varies from [Formula] psec to [Formula] nsec. Especially, water molecules, exhibiting ultraslow relaxation ([Formula] nsec) in the active state, are found around the microswitch residues that are considered activity hotspots for GPCR function. A continuous allosteric network spanning the TM domain, arising from water-mediated contacts, is unique in the active state, underscoring the importance of slow waters in the GPCR activation.

Biophysics↗

bioRxiv2016

Contact statistics highlight distinct organizing principles of proteins and RNA

Although both RNA and proteins have densely packed native structures, chain organizations of these two biopolymers are fundamentally different. Motivated by the recent discoveries in chromatin folding that interphase chromosomes have territorial organization with signatures pointing to metastability, we analyzed the biomolecular structures deposited in the Protein Data Bank and found that the intrachain contact probabilities, P(s) as a function of the arc length s, decay in power-law ~ s-{gamma} over the intermediate range of s, 10 [lsim] s [lsim] 110. We found that the contact probability scaling exponent is{gamma} {approx} 1.11 for large RNA (N > 110),{gamma} {approx} 1.41 for small sized RNA (N < 110), and{gamma} {approx} 1.65 for proteins. Given that Gaussian statistics is expected for a fully equilibrated chain in polymer melts, the deviation of{gamma} value from{gamma} = 1.5 for the subchains of large RNA in the native state suggests that the chain configuration of RNA is not fully equilibrated. It is visually clear that folded structures of large sized RNA (N {gtrsim} 110) adopt crumpled structures, partitioned into modular multi-domains assembled by proximal sequences along the chain, whereas the polypeptide chain of folded proteins looks better mixed with the rest of the structure. Our finding of{gamma} {approx} 1 for large RNA might be an ineluctable consequence of the hierarchical ordering of the secondary to tertiary elements in the folding process.

Biophysics↗