A Bottom-Up Coarse-Grained Model for Nucleosome–Nucleosome Interactions with Explicit Ions

Sun, Tiedong; Minhas, Vishal; Mirzoev, Alexander; Korolev, Nikolay; Lyubartsev, Alexander P.; Nordenskiöld, Lars

doi:10.1021/acs.jctc.2c00083

Cited by 16 publications

(20 citation statements)

References 69 publications

(159 reference statements)

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“…For instance, although recent physics-based and ML potentials appear extremely promising, it remains challenging to accurately model hierarchical biomolecular structures without invoking elastic network or Go ̅ type potentials. 32,143 As suggested in Figure 1, bottom-up methods are often perceived as appetizing, but impractical approaches that require resources, capabilities, and experience that are not accessible to "non-expert" users. It is worth noting that almost ten years the pragmatic Martini model was already employed to study the organization of lipid membranes consisting of more than 60 distinct types of lipids.…”

Section: Emergent Challenges and Promising Directionsmentioning

confidence: 99%

“…It is worth noting that almost ten years the pragmatic Martini model was already employed to study the organization of lipid membranes consisting of more than 60 distinct types of lipids. 402 While Voth and co-workers recently employed bottom-up methods in developing a CG model for the coronavirus capsid 5 and Lyubartsev and co-workers recently developed a bottom-up model for nucelosomal self-assembly, 143 one may reasonably ask when�and for what systems�the…”

Section: Emergent Challenges and Promising Directionsmentioning

confidence: 99%

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Perspective: Advances, Challenges, and Insight for Predictive Coarse-Grained Models

Noid

2023

J. Phys. Chem. B

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By averaging over atomic details, coarse-grained (CG) models provide profound computational and conceptual advantages for studying soft materials. In particular, bottom-up approaches develop CG models based upon information obtained from atomically detailed models. At least in principle, a bottom-up model can reproduce all the properties of an atomically detailed model that are observable at the resolution of the CG model. Historically, bottom-up approaches have accurately modeled the structure of liquids, polymers, and other amorphous soft materials, but have provided lower structural fidelity for more complex biomolecular systems. Moreover, they have also been plagued by unpredictable transferability and a poor description of thermodynamic properties. Fortunately, recent studies have reported dramatic advances in addressing these prior limitations. This Perspective reviews this remarkable progress, while focusing on its foundation in the basic theory of coarse-graining. In particular, we describe recent insights and advances for treating the CG mapping, for modeling many-body interactions, for addressing the state-point dependence of effective potentials, and even for reproducing atomic observables that are beyond the resolution of the CG model. We also outline outstanding challenges and promising directions in the field. We anticipate that the synthesis of rigorous theory and modern computational tools will result in practical bottom-up methods that not only are accurate and transferable but also provide predictive insight for complex systems.

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Section: Emergent Challenges and Promising Directionsmentioning

confidence: 99%

Section: Emergent Challenges and Promising Directionsmentioning

confidence: 99%

Perspective: Advances, Challenges, and Insight for Predictive Coarse-Grained Models

Noid

2023

J. Phys. Chem. B

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“…The nucleosome–nucleosome attraction could be regulated by the surrounding ion concentration. Sun et al began to simulate the effect of multivalent cations for systems comprising 20 nucleosome core particles, and the results of the coarse-grained (CG) model simulation revealed that the participation of positively-charged histone tails and multivalent (Mg 2+ , Co 3+ ) and monovalent (K + ) ions was necessary for DNA–DNA and core–core interactions and enabled the close stacking of nucleosomes [ 130 ]. Andreeva et al further compared the effects of Na + and K + ions on nucleosome structure, stability, and interactions with proteins.…”

Section: Multiple Regulatory Factors and Associated Mechanismmentioning

confidence: 99%

Studies of the Mechanism of Nucleosome Dynamics: A Review on Multifactorial Regulation from Computational and Experimental Cases

2023

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The nucleosome, which organizes the long coil of genomic DNA in a highly condensed, polymeric way, is thought to be the basic unit of chromosomal structure. As the most important protein–DNA complex, its structural and dynamic features have been successively revealed in recent years. However, its regulatory mechanism, which is modulated by multiple factors, still requires systemic discussion. This study summarizes the regulatory factors of the nucleosome’s dynamic features from the perspective of histone modification, DNA methylation, and the nucleosome-interacting factors (transcription factors and nucleosome-remodeling proteins and cations) and focuses on the research exploring the molecular mechanism through both computational and experimental approaches. The regulatory factors that affect the dynamic features of nucleosomes are also discussed in detail, such as unwrapping, wrapping, sliding, and stacking. Due to the complexity of the high-order topological structures of nucleosomes and the comprehensive effects of regulatory factors, the research on the functional modulation mechanism of nucleosomes has encountered great challenges. The integration of computational and experimental approaches, the construction of physical modes for nucleosomes, and the application of deep learning techniques will provide promising opportunities for further exploration.

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“… 12 , 13 The CHARMM force field is being used much less frequently, with an important exception of nucleosomes. 14 − 16 …”

Section: Introductionmentioning

confidence: 99%

“…Usually, the researchers choose the AMBER force field. This force field allows simulating complexes even with highly deformed DNA (with kinks as a result of protein intercalation), for example, in cases of Sox protein, − Hbb, , Sac7d, − LacI, and the others. , The CHARMM force field is being used much less frequently, with an important exception of nucleosomes. − …”

Section: Introductionmentioning

confidence: 99%

C–B–A Test of DNA Force Fields

et al. 2023

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The DNA duplex may be locally strongly bent in complexes with proteins, for example, with polymerases or in a nucleosome. At such bends, the DNA helix is locally in the noncanonical forms A (with a narrow major groove and a large amount of north sugars) or C (with a narrow minor groove and a large share of BII phosphates). To model the formation of such complexes by molecular dynamics methods, the force field is required to reproduce these conformational transitions for a naked DNA. We analyzed the available experimental data on the B–C and B–A transitions under the conditions easily implemented in modeling: in an aqueous NaCl solution. We selected six DNA duplexes which conformations at different salt concentrations are known reliably enough. At low salt concentrations, poly(GC) and poly(A) are in the B-form, classical and slightly shifted to the A-form, respectively. The duplexes ATAT and GGTATACC have a strong and salt concentration dependent bias toward the A-form. The polymers poly(AC) and poly(G) take the C- and A-forms, respectively, at high salt concentrations. The reproduction of the behavior of these oligomers can serve as a test for the balance of interactions between the base stacking and the conformational flexibility of the sugar–phosphate backbone in a DNA force field. We tested the AMBER bsc1 and CHARMM36 force fields and their hybrids, and we failed to reproduce the experiment. In all the force fields, the salt concentration dependence is very weak. The known B-philicity of the AMBER force field proved to result from the B-philicity of its excessively strong base stacking. In the CHARMM force field, the B-form is a result of a fragile balance between the A-philic base stacking (especially for G:C pairs) and the C-philic backbone. Finally, we analyzed some recent simulations of the LacI-, SOX-4-, and Sac7d-DNA complex formation in the framework of the AMBER force field.

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A Bottom-Up Coarse-Grained Model for Nucleosome–Nucleosome Interactions with Explicit Ions

Cited by 16 publications

References 69 publications

Perspective: Advances, Challenges, and Insight for Predictive Coarse-Grained Models

Perspective: Advances, Challenges, and Insight for Predictive Coarse-Grained Models

Studies of the Mechanism of Nucleosome Dynamics: A Review on Multifactorial Regulation from Computational and Experimental Cases

C–B–A Test of DNA Force Fields

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