arXiv subjects

Chun-Lai Ren

Publications and source records attributed to Chun-Lai Ren.

3 recordsLinked to original sources

arXiv2026

ATP-Independent Entropy-Driven dsRNA Unwinding by DDX3X Revealed by Coarse-Grained Simulations and Deep Learning

DEAD-box RNA helicases (DDXs) are traditionally known as ATP-dependent motors that unwind double-stranded RNA (dsRNA). Recent experiments, however, show that some DDXs promote dsRNA unwinding even in the absence of ATP, raising a fundamental question about the physical mechanism underlying ATP-independent strand separation. Here, we develop a minimal, physics-based coarse-grained RNA model and incorporate weak, specific interactions between DDX3X and dsRNA, revealing the inherently stochastic nature of unwinding events. The unwinding process must overcome an energy barrier, but thermal fluctuations and entropy gain provide a driving force for RNA remodeling. We identify that dsRNA separation proceeds through rare yet obligatory strand-displacing intermediates facilitated by DDX3X. By combining deep learning-assisted analysis, we further rank the contributions of different entropic components, revealing hydrogen bonding as the dominate factor, followed by base stacking and then the backbone conformation. These findings reveal a previously unrecognized physical mechanism for RNA duplex unwinding and offer an effective framework for studying RNA remodeling kinetics.

q-bio.BM↗

arXiv2022

Uncovering the molecular mechanism for dual effect of ATP on phase separation in FUS solution

Recent studies reported that adenosine triphosphate (ATP) could inhibit as well as enhance the phase separation in prion-like proteins. The molecular mechanism underlying such a puzzling phenomenon remains elusive. Here, taking the fused in sarcoma (FUS) solution as an example, we comprehensively reveal the underlying mechanism by which ATP regulates phase separation by combining the semiempirical quantum mechanical method, mean-field theory, and molecular simulation. At the microscopic level, ATP acts as a bivalent or trivalent binder; at the macroscopic level, the reentrant phase separation indeed occurs in dilute FUS solutions, resulting from the ATP-concentration--dependent binding ability under different conditions. Importantly, the ATP concentration for dissolving the protein condensates is about 10 mM, agreeing with experimental results. Furthermore, from a dynamic point of view, the effect of ATP on phase separation is also non-monotonic. This work provides a clear physical description of the microscopic interaction and macroscopic phase diagram of the ATP-modulated phase separation.

cond-mat.soft↗

arXiv2007

Structure and organization in inclusion-containing bilayer membranes

Membrane organization is essential for cellular functions such as signal transduction and membrane trafficking. A major challenge is to understand the lateral heterogeneous structures in membranes and membrane fluidity in the presence of inclusions. Based on a considerable amount of experimental evidence for lateral organization of lipid membranes which share astonishingly similar features in the presence of different inclusions, we first present a general model system of bilayer membranes embedded by nanosized inclusions, and explain experimental findings. Here, the hydrophobic inclusions are simple models of intrinsic membrane proteins, cholesterol embedded in the membrane, hydrophobic drugs, or other nanoparticles for bio-medical applications. It is found that lipid/inclusion-rich raft domains are formed at moderate inclusion concentrations, and disappear with the increase of inclusions. At high inclusion content, chaining of inclusions occurs due to the effective attraction between inclusions mediated by lipids. Meanwhile, increasing inclusions can also cause thickening of the membrane, and the distribution of inclusions undergoes a layering transition from one-layer located in the bilayer midplane to two-layer structure arranged into the two leaflets of a bilayer. Our theoretical predictions address the complex interactions between membranes and inclusions, suggesting a unifying mechanism which reflects the competition between the conformational entropy of lipids favoring the formation of lipid-rich rafts and the steric repulsion of inclusions leading to the uniform dispersion.

cond-mat.soft↗