The impact of charge regulation and ionic intranuclear environment on the nucleosome core particle DOI
Rikkert J. Nap, Paola Carrillo Gonzalez, A. E. Coraor

и другие.

The Journal of Chemical Physics, Год журнала: 2024, Номер 161(23)

Опубликована: Дек. 20, 2024

We theoretically investigate how the intranuclear environment influences charge of a nucleosome core particle (NCP)—the fundamental unit chromatin consisting DNA wrapped around histone proteins. The molecular-based theory explicitly considers size, shape, conformation, charge, and chemical state all molecular species—thereby linking structural with chemical/charged system. variations in monovalent divalent salt concentrations, as well pH, affect distribution across different regions an NCP quantify impact regulation. effective emerges from delicate complex balance involving dissociation equilibrium amino acids DNA-phosphates, electrostatic interaction between them, translational entropy mobile solution ions, i.e., counter ion release condensation. From our results, we note significant effect magnesium ions on energy counterion cloud that surrounds NCP. As function concentration, neutralization, even inversion is predicted—in line experimental observation NCPs. strong Mg-dependence arises bridges two DNA-phosphates one Mg2+ ion. demonstrate to describe predict charged properly, it essential consider details, such DNA-phosphate condensation acid–base comprise

Язык: Английский

Interpretable Protein-DNA Interactions Captured by Structure-based Optimization DOI Creative Commons

Yafan Zhang,

Irene Silvernail,

Zhuyang Lin

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Май 27, 2024

Abstract Sequence-specific DNA recognition underlies essential processes in gene regulation, yet methods for simultaneous prediction of genomic sites and their binding affinity remain lacking. Here, we present the Interpretable protein-DNA Energy Associative (IDEA) model, a residue-level, interpretable biophysical model capable predicting affinities DNA-binding proteins. By fusing structures sequences known complexes into an optimized energy IDEA enables direct interpretation physicochemical interactions among individual amino acids nucleotides. We demonstrate that this can accurately predict strengths across various protein families. Additionally, is integrated coarse-grained simulation framework quantitatively captures absolute free energies. Overall, provides computational platform alleviating experimental costs biases assessing be utilized mechanistic studies DNA-recognition processes.

Язык: Английский

Процитировано

3
The shifting paradigm of chromatin structure: from the 30-nm chromatin fiber to liquid-like organization DOI Creative Commons
Kazuhiro Maeshima

Proceedings of the Japan Academy Series B, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

The organization and dynamics of chromatin are critical for genome functions such as transcription DNA replication/repair. Historically, was assumed to fold into the 30-nm fiber progressively arrange larger helical structures, described in textbook model. However, over past 15 years, extensive evidence including our studies has dramatically transformed view from a static, regular structure one that is more variable dynamic. In higher eukaryotic cells, forms condensed yet liquid-like domains, which appear be basic unit structure, replacing fiber. These domains maintain proper accessibility, ensuring regulation reaction processes. During mitosis, these assemble form gel-like mitotic chromosomes, further constrained by condensins other factors. Based on available evidence, I discuss physical properties live emphasizing its viscoelastic nature-balancing local fluidity with global stability support functions.

Язык: Английский

Процитировано

0
Toward decoding the mechanisms that shape sub-megabase-scale genome organization DOI
Joseph M. Paggi, Bin Zhang

Current Opinion in Structural Biology, Год журнала: 2025, Номер 92, С. 103062 - 103062

Опубликована: Май 8, 2025

Язык: Английский

Процитировано

0
Current Advances in Genome Modeling Across Length Scales DOI Creative Commons
E Schultz, Joseph Kaplan, Yiheng Wu

и другие.

Wiley Interdisciplinary Reviews Computational Molecular Science, Год журнала: 2025, Номер 15(3)

Опубликована: Май 1, 2025

ABSTRACT The physical organization of DNA within the nucleus is fundamental to a wide range biological processes. experimental investigation structure genomic remains challenging due its large size and hierarchical arrangement. These challenges present considerable opportunities for combined modeling approaches. Physics‐based computational models, in particular, have emerged as essential tools probing chromatin dynamics across length scales. Such models must necessarily be capable bridging scales, each scale presents own subtleties intricacies. This review discusses recent methodological advances structural modeling, emphasizing need multiscale integration capture molecular mechanisms that underlie function. We an analysis state‐of‐the‐art methods, well perspective on future scales ranging from bare nucleosomes fibers, up TAD chromosome‐scale models. emphasize connect genome gene expression, leverage emerging machine learning capabilities, develop examine gaps data are poised address propose directions research bridge theory experiment biology.

Язык: Английский

Процитировано

0
The Impact of Charge Regulation and Ionic Intranuclear Environment on the Nucleosome Core Particle DOI Creative Commons
Rikkert J. Nap, Paola Carrillo Gonzalez, A. E. Coraor

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Ноя. 12, 2024

We theoretically investigate how the intranuclear environment influences charge of a nucleosome core particle (NCP) - fundamental unit chromatin consisting DNA wrapped around histone proteins. The molecular-based theory explicitly considers size, shape, conformations, charges, and chemical states all molecular species thereby linking structural state with chemical/charged system. variations in monovalent divalent salt concentrations, as well pH, affect distribution across different regions an NCP quantify impact regulation. effective emerges from delicate complex balance involving dissociation equilibrium amino acids DNA-phosphates, electrostatic interaction between them, translational entropy mobile solution ions, i.e., counter ion release condensation. From our results, we note significant effect magnesium ions on energy counterion cloud that surrounds NCP, function concentration, neutralization, even inversion is predicted line experimental observation NCPs. strong Mg-dependence arises bridges two DNA-phosphates one Mg

Язык: Английский

Процитировано

0
The impact of charge regulation and ionic intranuclear environment on the nucleosome core particle DOI
Rikkert J. Nap, Paola Carrillo Gonzalez, A. E. Coraor

и другие.

The Journal of Chemical Physics, Год журнала: 2024, Номер 161(23)

Опубликована: Дек. 20, 2024

We theoretically investigate how the intranuclear environment influences charge of a nucleosome core particle (NCP)—the fundamental unit chromatin consisting DNA wrapped around histone proteins. The molecular-based theory explicitly considers size, shape, conformation, charge, and chemical state all molecular species—thereby linking structural with chemical/charged system. variations in monovalent divalent salt concentrations, as well pH, affect distribution across different regions an NCP quantify impact regulation. effective emerges from delicate complex balance involving dissociation equilibrium amino acids DNA-phosphates, electrostatic interaction between them, translational entropy mobile solution ions, i.e., counter ion release condensation. From our results, we note significant effect magnesium ions on energy counterion cloud that surrounds NCP. As function concentration, neutralization, even inversion is predicted—in line experimental observation NCPs. strong Mg-dependence arises bridges two DNA-phosphates one Mg2+ ion. demonstrate to describe predict charged properly, it essential consider details, such DNA-phosphate condensation acid–base comprise

Язык: Английский

Процитировано

0