scholarly journals Histone dynamics mediate DNA unwrapping and sliding in nucleosomes: insights from multi-microsecond molecular dynamics simulations

2021 ◽  
Author(s):  
Grigoriy A. Armeev ◽  
Anastasia S. Kniazeva ◽  
Galina A. Komarova ◽  
Mikhail P. Kirpichnikov ◽  
Alexey K. Shaytan
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Building Blocks ◽  
Dna Dynamics ◽  
Conformational Variability ◽  
Nucleosome Core ◽  
Nucleosome Dynamics ◽  
Nucleosomal Dna ◽  
Dna Unwrapping ◽  
Dynamics Simulations

AbstractNucleosomes are elementary building blocks of chromatin in eukaryotes. They tightly wrap ~147 DNA base pairs around an octamer of histone proteins. How nucleosome structural dynamics affect genome functioning is not completely clear. Here we report all-atom molecular dynamics simulations of nucleosome core particles at a timescale of 15 microseconds. At this timescale, functional modes of nucleosome dynamics such as spontaneous nucleosomal DNA breathing, unwrapping, twisting, and sliding were observed. We identified atomistic mechanisms of these processes by analyzing the accompanying structural rearrangements of the histone octamer and histone-DNA contacts. Octamer dynamics and plasticity were found to enable DNA unwrapping and sliding. Through multi-scale modeling, we showed that nucle-osomal DNA dynamics contribute to significant conformational variability of the chromatin fiber at the supranucleosomal level. Our study further supports mechanistic coupling between fine details of histone dynamics and chromatin functioning, provides a framework for understanding the effects of various chromatin modifications.We developed a web site for an interactive preview of molecular dynamics trajectories at https://intbio.github.io/Armeev_et_al_2021.

scholarly journals Histone dynamics mediate DNA unwrapping and sliding in nucleosomes

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Grigoriy A. Armeev ◽  
Anastasiia S. Kniazeva ◽  
Galina A. Komarova ◽  
Mikhail P. Kirpichnikov ◽  
Alexey K. Shaytan
Keyword(s):  
Building Blocks ◽  
Dna Dynamics ◽  
Conformational Variability ◽  
Nucleosome Core ◽  
Nucleosome Dynamics ◽  
Nucleosome Core Particles ◽  
Nucleosomal Dna ◽  
Dna Base ◽  
Dna Unwrapping ◽  
Dynamics Simulations

AbstractNucleosomes are elementary building blocks of chromatin in eukaryotes. They tightly wrap ∼147 DNA base pairs around an octamer of histone proteins. How nucleosome structural dynamics affect genome functioning is not completely clear. Here we report all-atom molecular dynamics simulations of nucleosome core particles at a timescale of 15 microseconds. At this timescale, functional modes of nucleosome dynamics such as spontaneous nucleosomal DNA breathing, unwrapping, twisting, and sliding were observed. We identified atomistic mechanisms of these processes by analyzing the accompanying structural rearrangements of the histone octamer and histone-DNA contacts. Octamer dynamics and plasticity were found to enable DNA unwrapping and sliding. Through multi-scale modeling, we showed that nucleosomal DNA dynamics contribute to significant conformational variability of the chromatin fiber at the supranucleosomal level. Our study further supports mechanistic coupling between fine details of histone dynamics and chromatin functioning, provides a framework for understanding the effects of various chromatin modifications.

scholarly journals Dynamic regulation of HIV-1 capsid interaction with the restriction factor TRIM5α identified by magic-angle spinning NMR and molecular dynamics simulations

2018 ◽  
Vol 115 (45) ◽  
pp. 11519-11524 ◽  
Author(s):  
Caitlin M. Quinn ◽  
Mingzhang Wang ◽  
Matthew P. Fritz ◽  
Brent Runge ◽  
Jinwoo Ahn ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Building Blocks ◽  
Magic Angle Spinning ◽  
Magic Angle ◽  
Capsid Assembly ◽  
Dynamic Regulation ◽  
Angle Spinning ◽  
Dynamics Simulations ◽  
Hiv 1

The host factor protein TRIM5α plays an important role in restricting the host range of HIV-1, interfering with the integrity of the HIV-1 capsid. TRIM5 triggers an antiviral innate immune response by functioning as a capsid pattern recognition receptor, although the precise mechanism by which the restriction is imposed is not completely understood. Here we used an integrated magic-angle spinning nuclear magnetic resonance and molecular dynamics simulations approach to characterize, at atomic resolution, the dynamics of the capsid’s hexameric and pentameric building blocks, and the interactions with TRIM5α in the assembled capsid. Our data indicate that assemblies in the presence of the pentameric subunits are more rigid on the microsecond to millisecond timescales than tubes containing only hexamers. This feature may be of key importance for controlling the capsid’s morphology and stability. In addition, we found that TRIM5α binding to capsid induces global rigidification and perturbs key intermolecular interfaces essential for higher-order capsid assembly, with structural and dynamic changes occurring throughout the entire CA polypeptide chain in the assembly, rather than being limited to a specific protein-protein interface. Taken together, our results suggest that TRIM5α uses several mechanisms to destabilize the capsid lattice, ultimately inducing its disassembly. Our findings add to a growing body of work indicating that dynamic allostery plays a pivotal role in capsid assembly and HIV-1 infectivity.

scholarly journals DNA methylation cues in nucleosome geometry, stability, and unwrapping

2021 ◽  
Author(s):  
Shuxiang Li ◽  
Yunhui Peng ◽  
David Landsman ◽  
Anna Panchenko
Keyword(s):  
Conformational Changes ◽  
Cytosine Methylation ◽  
Epigenetic Mark ◽  
Nucleosome Assembly ◽  
Functional Studies ◽  
Nucleosome Dynamics ◽  
Nucleosomal Dna ◽  
Dna Unwrapping ◽  
Dynamics Simulations ◽  
Eukaryotic Organisms

Cytosine methylation at the 5-carbon position is an essential DNA epigenetic mark in many eukaryotic organisms. Although countless structural and functional studies of cytosine methylation have been reported in both prokaryotes and eukaryotes, our understanding of how it influences the nucleosome assembly, structure, and dynamics remains obscure. Here we investigated the effects of cytosine methylation at CpG sites on nucleosome dynamics and stability. By applying long molecular dynamics simulations (five microsecond long trajectories, 60 microseconds in total), we generated extensive atomic level conformational full nucleosome ensembles. Our results revealed that methylation induces pronounced changes in geometry for both linker and nucleosomal DNA, leading to a more curved, under-twisted DNA, shifting the population equilibrium of sugar-phosphate backbone geometry. These conformational changes are associated with a considerable enhancement of interactions between methylated DNA and the histone octamer, doubling the number of contacts at some key arginines. H2A and H3 tails play important roles in these interactions, especially for DNA methylated nucleosomes. This, in turn, prevents a spontaneous DNA unwrapping of 3-4 helical turns for the methylated nucleosome with truncated histone tails, otherwise observed in the unmethylated system on several microsecond time scale.

scholarly journals Coarse-Grained Molecular Dynamics Simulations of Nanoplastics Interacting with a Hydrophobic Environment in Aqueous Solution

2021 ◽  
Author(s):  
Lorenz Dettmann ◽  
Oliver Kühn ◽  
Ashour A. Ahmed
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Functional Groups ◽  
Critical Role ◽  
Terrestrial Ecosystems ◽  
Building Blocks ◽  
Coarse Grained ◽  
Hydrophobic Polymers ◽  
Dynamics Simulations ◽  
Coarse Grained Molecular Dynamics

<div><div><div><p>Nanoplastics (NPs) are emerging threats for marine and terrestrial ecosystems, but little is known about their fate in the environment at the molecular scale. In this work, coarse-grained molecular dynamics simulations were performed to investigate nature and strength of the interaction between NPs and hydrophobic environments. Specifically, NPs were simulated with different hydrophobic and hydrophilic polymers while carbon nanotubes (CNTs) were used to mimic surface and confinement effects of hydrophobic building blocks occurring in a soil environment. The hydrophobicity of CNTs was modified by introducing different hydrophobic and hydrophilic functional groups at their inner surfaces. The results show that hydrophobic polymers have a strong affinity to adsorb at the outer surface and to be captured inside the CNT. The accumulation within the CNT is even increased in presence of hydrophobic functional groups. This contribution is a first step towards a mechanistic understanding of a variety of processes connected to interaction of nanoscale material with environmental systems. Regarding the fate of NPs in soil, the results point to the critical role of the hydrophobicity of NPs and soil organic matter (SOM) as well as of the chemical nature of functionalized SOM cavities/voids in controlling the accumulation of NPs in soil. Moreover, the results can be related to water treatment technologies as it is shown that the hydrophobicity of CNTs and functionalization of their surfaces may play a crucial role in enhancing the adsorption capacity of CNTs with respect to organic compounds and thus their removal efficiency from wastewater.</p><p><br></p></div></div></div>

scholarly journals Coarse-Grained Molecular Dynamics Simulations of Nanoplastics Interacting with a Hydrophobic Environment in Aqueous Solution

2021 ◽  
Author(s):  
Lorenz Dettmann ◽  
Oliver Kühn ◽  
Ashour A. Ahmed
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Functional Groups ◽  
Critical Role ◽  
Terrestrial Ecosystems ◽  
Building Blocks ◽  
Coarse Grained ◽  
Hydrophobic Polymers ◽  
Dynamics Simulations ◽  
Coarse Grained Molecular Dynamics

<div><div><div><p>Nanoplastics (NPs) are emerging threats for marine and terrestrial ecosystems, but little is known about their fate in the environment at the molecular scale. In this work, coarse-grained molecular dynamics simulations were performed to investigate nature and strength of the interaction between NPs and hydrophobic environments. Specifically, NPs were simulated with different hydrophobic and hydrophilic polymers while carbon nanotubes (CNTs) were used to mimic surface and confinement effects of hydrophobic building blocks occurring in a soil environment. The hydrophobicity of CNTs was modified by introducing different hydrophobic and hydrophilic functional groups at their inner surfaces. The results show that hydrophobic polymers have a strong affinity to adsorb at the outer surface and to be captured inside the CNT. The accumulation within the CNT is even increased in presence of hydrophobic functional groups. This contribution is a first step towards a mechanistic understanding of a variety of processes connected to interaction of nanoscale material with environmental systems. Regarding the fate of NPs in soil, the results point to the critical role of the hydrophobicity of NPs and soil organic matter (SOM) as well as of the chemical nature of functionalized SOM cavities/voids in controlling the accumulation of NPs in soil. Moreover, the results can be related to water treatment technologies as it is shown that the hydrophobicity of CNTs and functionalization of their surfaces may play a crucial role in enhancing the adsorption capacity of CNTs with respect to organic compounds and thus their removal efficiency from wastewater.</p><p><br></p></div></div></div>

scholarly journals How a Hemicarcerand Incarcerates Guests at Room Temperature Decoded with Modular Simulations

2020 ◽  
Author(s):  
Katherine G. McFerrin ◽  
Yuan-Ping Pang
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Model Building ◽  
Three Dimensional ◽  
Building Blocks ◽  
Water Soluble ◽  
Modular Approach ◽  
Molecular Complexation ◽  
Three Dimensional Models ◽  
Dynamics Simulations

AbstractHemicarcerands are host molecules created to study constrictive binding with guest molecules for insights into the rules of molecular complexation. However, the molecular dynamics simulations that facilitate such studies have been limited because three-dimensional models of hemicarcerands are tedious to build and their atomic charges are complicated to derive. There have been no molecular dynamics simulations of the reported water-soluble hemicarcerand (Octacid4) that explain how it uniquely encapsulates its guests at 298 K and keeps them encapsulated at 298 K in NMR experiments. Herein we report a modular approach to hemicarcerand simulations that simplifies the model building and charge derivation in a manner reminiscent of the approach to protein simulations with truncated amino acids as building blocks. We also report that apo Octacid4 in water adopts two clusters of conformations, one of which has an equatorial portal open thus allowing guests to enter the cavity of Octacid4, in microsecond molecular dynamics simulations performed using the modular approach at 298 K. Under the same simulation conditions, the guest-bound Octacid4 adopts one cluster of conformations with all equatorial portals closed thus keeping the guests incarcerated. These results explain the unique constrictive binding of Octacid4 and suggest that the guest-induced host conformational change that impedes decomplexation is a previously unrecognized conformational characteristic that promotes strong molecular complexation.

Following the Crystal Growth of Anthradithiophenes through Atomistic Molecular Dynamics Simulations and Graph Characterization

2022 ◽  
Author(s):  
Sean M. Ryno ◽  
Ramin Noruzi ◽  
Chamikara Karunasena ◽  
Balaji Sesha Sarath Pokuri ◽  
Shi Li ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Crystal Growth ◽  
Molecular Dynamics Simulations ◽  
Organic Semiconductors ◽  
Building Blocks ◽  
Nucleation And Growth ◽  
Distinctive Features ◽  
Molecular Building Blocks ◽  
Dynamics Simulations

While organic semiconductors (OSC) offer distinctive features for several electronic and optical technologies, questions remain as to how the chemistries of the molecular building blocks impact material nucleation and growth...

scholarly journals Dissecting DNA-Histone Interactions in the Nucleosome by Molecular Dynamics Simulations of DNA Unwrapping

2011 ◽  
Vol 101 (8) ◽  
pp. 1999-2008 ◽  
Author(s):  
Ramona Ettig ◽  
Nick Kepper ◽  
Rene Stehr ◽  
Gero Wedemann ◽  
Karsten Rippe
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Dna Unwrapping ◽  
Dynamics Simulations

scholarly journals DNA translocase repositions a nucleosome by the lane-switch mechanism

2021 ◽  
Author(s):  
Fritz Nagae ◽  
Giovanni B. Brandani ◽  
Shoji Takada ◽  
Tsuyoshi Terakawa
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Deep Sequencing ◽  
Restriction Enzyme ◽  
Enzyme Digestion ◽  
Coarse Grained ◽  
Restriction Enzyme Digestion ◽  
Nucleosomal Dna ◽  
Dynamics Simulations ◽  
Histone Core

ABSTRACTTranslocases such as DNA/RNA polymerases, replicative helicases, and exonucleases are involved in eukaryotic DNA transcription, replication, and repair. Since eukaryotic genomic DNA wraps around histone core complexes and forms nucleosomes, translocases inevitably encounter nucleosomes. Previous studies have shown that a histone core complex repositions upstream (downstream) when SP6RNA or T7 RNA polymerase (bacterial exonuclease, RecBCD) partially unwraps nucleosomal DNA. However, the molecular mechanism of the downstream repositioning remains unclear. In this study, we identify the lane-shift mechanism for downstream nucleosome repositioning via coarse-grained molecular dynamics simulations, which we validated by restriction enzyme digestion assays and deep sequencing assays. In this mechanism, after a translocase unwraps nucleosomal DNA up to the site proximal to the dyad, the remaining wrapped DNA switches its binding region (lane) to that vacated by the unwrapping, and the downstream DNA rewraps, completing downstream repositioning. This mechanism may have crucial implications for transcription through nucleosomes, histone recycling, and nucleosome remodeling.SIGNIFICANCEEukaryotic chromosomes are composed of repeating subunits termed nucleosomes. Thus, proteins that translocate along the chromosome, DNA translocases, inevitably collide with nucleosomes. Previous studies revealed that a translocase repositions a nucleosome upstream or downstream upon their collision. Though the molecular mechanisms of the upstream repositioning have been extensively studied, that of downstream repositioning remains elusive. In this study, we performed coarse-grained molecular dynamics simulations, proposed the lane-shift mechanism for downstream repositioning, and validated this mechanism by restriction enzyme digestion assays and deep sequencing assays. This mechanism has broad implications for how translocases deal with nucleosomes for their functions.

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