arXiv subjects

Sucheol Shin

Publications and source records attributed to Sucheol Shin.

8 recordsLinked to original sources

arXiv2025

Static Three-Dimensional Structures Determine Fast Dynamics Between Distal Loci Pairs in Interphase Chromosomes

Live-cell imaging experiments have shown that the distal dynamics between enhancers and promoters are unexpectedly rapid and incompatible with standard polymer models. The discordance between the compact static chromatin organization and dynamics is a conundrum that violates the expected structure-function relationship. We developed a theory to predict chromatin dynamics by accurately determining three-dimensional (3D) structures from static Hi-C contact maps or fixed-cell imaging data. Using the calculated 3D coordinates, the theory accurately forecasts experimentally observed two-point chromatin dynamics. It predicts rapid enhancer-promoter interactions and uncovers a scaling relationship between two-point relaxation time and genomic separation, closely matching recent measurements. The theory predicts that cohesin depletion accelerates single-locus diffusion while significantly slowing relaxation dynamics within topologically associating domains (TADs). Our results demonstrate that chromatin dynamics can be reliably inferred from static structural data, reinforcing the notion that 3D chromatin structure governs dynamic behavior. This general framework offers powerful tools for exploring chromatin dynamics across diverse biological contexts.

physics.bio-ph↗

arXiv2024

Organization and Dynamics of Chromosomes

How long threadlike eukaryotic chromosomes fit tidily in the small volume of the nucleus without significant entanglement is just beginning to be understood, thanks to major advances in experimental techniques. Several polymer models, which reproduce contact maps that measure the probabilities that two loci are in spatial contact, have predicted the three-dimensional structures of interphase chromosomes. Data-driven approaches, using contact maps as input, predict that mitotic helical chromosomes are characterized by switch in handedness, referred to as "perversion". By using experimentally derived effective interactions between chromatin loci in simulations, structures of conventional and inverted nuclei have been accurately predicted. Polymer theory and simulations show that the dynamics of individual loci in chromatin exhibit subdiffusive behavior but the diffusion exponents are broadly distributed, which accords well with experiments. Although coarse-grained models are successful, many challenging problems remain, which require the creation of new experimental and computational tools to understand genome biology.

cond-mat.soft↗

arXiv2024

Transcription-induced active forces suppress chromatin motion

The organization of interphase chromosomes in a number of species is starting to emerge thanks to advances in a variety of experimental techniques. However, much less is known about the dynamics, especially in the functional states of chromatin. Some experiments have shown that the motility of individual loci in human interphase chromosome decreases during transcription, and increases upon inhibiting transcription. This is a counter-intuitive finding because it is thought that the active mechanical force ($F$) on the order of ten pico-newtons, generated by RNA polymerase II (RNAPII) that is presumably transmitted to the gene-rich region of the chromatin, would render it more open, thus enhancing the mobility. We developed a minimal active copolymer model for interphase chromosomes to investigate how $F$ affects the dynamical properties of chromatin. The movements of the loci in the gene-rich region are suppressed in an intermediate range of $F$, and are enhanced at small $F$ values, which has also been observed in experiments. In the intermediate $F$, the bond length between consecutive loci increases, becoming commensurate with the distance at the minimum of the attractive interaction between non-bonded loci. This results in a transient disorder-to-order transition, leading to a decreased mobility during transcription. Strikingly, the $F$-dependent change in the locus dynamics preserves the organization of the chromosome at $F=0$. Transient ordering of the loci, which is not found in the polymers with random epigenetic profiles, in the gene-rich region might be a plausible mechanism for nucleating a dynamic network involving transcription factors, RNAPII, and chromatin.

physics.bio-ph↗

arXiv2023

From Effective Interactions Extracted Using Hi-C Data to Chromosome Structures in Conventional and Inverted Nuclei

Contact probabilities between loci, separated by arbitrary genomic distance, for a number of cell types have been reported using genome-wide chromosome conformation capture (Hi-C) experiments. How to extract the effective interaction energies between active euchromatin (A) and inactive heterochromatin (B) directly from the experimental data, without an underlying polymer model, is unsolved. Here, we first calculate the pairwise effective interaction energies (A-A, B-B, or A-B) for interphase chromosomes based on Hi-C data by using the concept of Statistical Potential (SP), which assumes that the interaction energy between two loci is proportional to the logarithm of the frequency with which they interact. Polymer simulations, using the extracted interaction energy values $\textit{without any parameter}$, reproduce the segregation between A and B type loci (compartments), and the emergence of topologically associating domains (TADs), features that are prominent in the Hi-C data for interphase chromosomes. Remarkably, the values of the SP automatically satisfy the Flory-Huggins phase separation criterion for all the chromosomes, which explains the mechanism of compartment formation in interphase chromosomes. Strikingly, simulations using the SP that accounts for pericentromeric constitutive heterochromatin (C-type), show hierarchical structuring with the high density of C-type loci in the nuclear center, followed by localization of the B type loci, with euchromatin being confined to the nuclear periphery, which differs from the expected nuclear organization of interphase chromosomes, but is in accord with the imaging data of the inverted nuclei found in photoreceptor rods in nocturnal mammals. The proposed parameter free method and applications show that compartment formation in conventional and inverted nuclei is best explained by the inequality between the effective interaction energies.

cond-mat.soft↗

arXiv2020

Water Dynamics Around Proteins: T- and R-States of Hemoglobin and Melittin

The water dynamics, as characterized by the local hydrophobicity (LH), is investigated for tetrameric hemoglobin and dimeric melittin. For the T0 to R0 transition in Hb it is found that LH provides additional molecular-level insight into the Perutz mechanism, i.e., the breaking and formation of salt bridges at the alpha1 / beta2 and alpha2 / beta1 interface is accompanied by changes in LH. For Hb in cubic water boxes with 90 Aengstroem and 120 Aengstroem edge length it is observed that following a decrease in LH as a consequence of reduced water density or change of water orientation at the protein/water interface the alpha / beta interfaces are destabilized; this is a hallmark of the Perutz stereochemical model for the T to R transition in Hb. The present work thus provides a dynamical view of the classical structural model relevant to the molecular foundations of Hb function. For dimeric melittin, earlier results by Cheng and Rossky (Nature, 1998, 392, 696-699) are confirmed and interpreted on the basis of LH from simulations in which the protein structure is frozen. For the flexible melittin dimer the changes in the local hydration can be as much as 30 % than for the rigid dimer, reflecting the fact that protein and water dynamics are coupled.

physics.chem-ph↗

arXiv2018

Water's interfacial hydrogen bonding structure reveals the effective strength of surface-water interactions

The interactions of a hydrophilic surface with water can significantly influence the characteristics of the liquid water interface. In this manuscript, we explore this influence by studying the molecular structure of liquid water at a disordered surface with tunable surface-water interactions. We combine all-atom molecular dynamics simulations with a mean field model of interfacial hydrogen bonding to analyze the effect of surface-water interactions on the structural and energetic properties of the liquid water interface. We find that the molecular structure of water at a weakly interacting (i.e., hydrophobic) surface is resistant to change unless the strength of surface-water interactions are above a certain threshold. We find that below this threshold water's interfacial structure is homogeneous and insensitive to the details of the disordered surface, however, above this threshold water's interfacial structure is heterogeneous. Despite this heterogeneity, we demonstrate that the equilibrium distribution of molecular orientations can be used to quantify the energetic component of the surface-water interactions that contribute specifically to modifying the interfacial hydrogen bonding network. We identify this specific energetic component as a new measure of hydrophilicity, which we refer to as the intrinsic hydropathy.

cond-mat.soft↗

arXiv2018

Three-body Hydrogen Bond Defects Contribute Significantly to the Dielectric Properties of the Liquid Water-Vapor Interface

In this Letter, we present a simple model of aqueous interfacial molecular structure and we use this model to isolate the effects of hydrogen bonding on the dielectric properties of the liquid water-vapor interface. By comparing this model to the results of atomistic simulation we show that the anisotropic distribution of molecular orientations at the interface can be understood by considering the behavior of a single water molecule interacting with the average interfacial density field via an empirical hydrogen bonding potential. We illustrate that the depth dependence of this orientational anisotropy is determined by the geometric constraints of hydrogen bonding and we show that the primary features of simulated orientational distributions can be reproduced by assuming an idealized, perfectly tetrahedral hydrogen bonding geometry. We also demonstrate that non-ideal hydrogen bond geometries are required to produce interfacial variations in the average orientational polarization and polarizability. We find that these interfacial properties contain significant contributions from a specific type of geometrically distorted three-body hydrogen bond defect that is preferentially stabilized at the interface. Our findings thus reveal that the dielectric properties of the liquid water-vapor interface are determined by collective molecular interactions that are unique to the interfacial environment.

cond-mat.soft↗

arXiv2017

Characterizing Hydration Properties Based on the Orientational Structure of Interfacial Water Molecules

In this manuscript, we present a general computational method for characterizing the molecular structure of liquid water interfaces as sampled from atomistic simulations. With this method, the interfacial structure is quantified based on the statistical analysis of the orientational configurations of interfacial water molecules. The method can be applied to generate position dependent maps of the hydration properties of heterogeneous surfaces. We present an application to the characterization of surface hydrophobicity, which we use to analyze simulations of a hydrated protein. We demonstrate that this approach is capable of revealing microscopic details of the collective dynamics of a protein hydration shell.

cond-mat.soft↗