Molecular dynamics of de novo telomere heterochromatin formation in budding yeast

AbstractThe budding yeast SIR complex (Silent Information Regulator) is the principal actor in heterochromatin formation, which causes epigenetically regulated gene silencing phenotypes. The maternal chromatin bound SIR complex is disassembled during replication. Consequently, if heterochromatin is to be restored on both daughter strands, the SIR complex has to be reformed on both strands to pre-replication levels. The dynamics of SIR complex maintenance and re-formation during the cell-cycle and in different growth conditions are however not clear. Understanding exchange rates of SIR subunits during the cell cycle and their distribution pattern to daughter chromatids after replication has important implications for how heterochromatic states may be inherited and therefore how epigenetic states are maintained from one cellular generation to the next. We used the tag switch RITE system to measure genome wide turnover rates of the SIR subunit Sir3 before and after exit from stationary phase and show that maternal Sir3 subunits are completely replaced with newly synthesized Sir3 at subtelomeric regions during the first cell cycle after release from stationary phase. The SIR complex is therefore not “inherited” and the silenced state has to be established de novo upon exit from stationary phase. Additionally, our analysis of genome-wide transcription dynamics shows that precise Sir3 dosage is needed for the optimal up-regulation of “growth” genes during the first cell-cycle after release from stationary phase.

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On the dynamics of some small structural motifs in rRNA upon ligand binding

Journal of the Serbian Chemical Society ◽

10.2298/jsc0801041r ◽

2008 ◽

Vol 73 (1) ◽

pp. 41-53

Author(s):

Aleksandra Rakic ◽

Petar Mitrasinovic

Keyword(s):

Molecular Dynamics ◽

Conformational Changes ◽

Binding Sites ◽

De Novo ◽

Reference Structure ◽

Base Pairs ◽

Rna Sequences ◽

Conformational Model ◽

Thermodynamic Variables ◽

Dynamics Simulations

The present study characterizes using molecular dynamics simulations the behavior of the GAA (1186-1188) hairpin triloops with their closing c-g base pairs in large ribonucleoligand complexes (PDB IDs: 1njn, 1nwy, 1jzx). The relative energies of the motifs in the complexes with respect to that in the reference structure (unbound form of rRNA; PDB ID: 1njp) display the trends that agree with those of the conformational parameters reported in a previous study1 utilizing the de novo pseudotorsional (?,?) approach. The RNA regions around the actual RNA-ligand contacts, which experience the most substantial conformational changes upon formation of the complexes were identified. The thermodynamic parameters, based on a two-state conformational model of RNA sequences containing 15, 21 and 27 nucleotides in the immediate vicinity of the particular binding sites, were evaluated. From a more structural standpoint, the strain of a triloop, being far from the specific contacts and interacting primarily with other parts of the ribosome, was established as a structural feature which conforms to the trend of the average values of the thermodynamic variables corresponding to the three motifs defined by the 15-, 21- and 27-nucleotide sequences. From a more functional standpoint, RNA-ligand recognition is suggested to be presumably dictated by the types of ligands in the complexes.

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De novo protein structure prediction using ultra-fast molecular dynamics simulation

PLoS ONE ◽

10.1371/journal.pone.0205819 ◽

2018 ◽

Vol 13 (11) ◽

pp. e0205819 ◽

Cited By ~ 6

Author(s):

Ngaam J. Cheung ◽

Wookyung Yu

Keyword(s):

Molecular Dynamics ◽

Protein Structure ◽

Molecular Dynamics Simulation ◽

Protein Structure Prediction ◽

Structure Prediction ◽

De Novo ◽

Dynamics Simulation

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A computational study on cannabinoid receptors and potent bioactive cannabinoid ligands: homology modeling, docking, de novo drug design and molecular dynamics analysis

Molecular Diversity ◽

10.1007/s11030-009-9166-4 ◽

2009 ◽

Vol 14 (2) ◽

pp. 257-276 ◽

Cited By ~ 26

Author(s):

Serdar Durdagi ◽

Manthos G. Papadopoulos ◽

Panagiotis G. Zoumpoulakis ◽

Catherine Koukoulitsa ◽

Thomas Mavromoustakos

Keyword(s):

Molecular Dynamics ◽

Drug Design ◽

Homology Modeling ◽

Cannabinoid Receptors ◽

De Novo ◽

Computational Study ◽

Dynamics Analysis ◽

De Novo Drug Design

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Reorganization of budding yeast cytoplasm upon energy depletion

Molecular Biology of the Cell ◽

10.1091/mbc.e20-02-0125 ◽

2020 ◽

Vol 31 (12) ◽

pp. 1232-1245 ◽

Cited By ~ 6

Author(s):

Guendalina Marini ◽

Elisabeth Nüske ◽

Weihua Leng ◽

Simon Alberti ◽

Gaia Pigino

Keyword(s):

Translational Control ◽

De Novo ◽

Budding Yeast ◽

Energy Depletion

Yeast responds to energy depletion with a rapid cytoplasmic reorganization that includes cytosol compaction and de novo formation of membraneless compartments. The reversible polymerization of eIF2B into filamentous assemblies suggests a mechanism of translational control that allows cells to move quickly back and forth between response states.

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Understanding the R882H mutation effects of DNA methyltransferase DNMT3A: a combination of molecular dynamics simulations and QM/MM calculations

RSC Advances ◽

10.1039/c9ra06791d ◽

2019 ◽

Vol 9 (54) ◽

pp. 31425-31434 ◽

Cited By ~ 1

Author(s):

Lanxuan Liu ◽

Ting Shi ◽

Kendall N. Houk ◽

Yi-Lei Zhao

Keyword(s):

Molecular Dynamics ◽

Molecular Dynamics Simulations ◽

Dna Methyltransferase ◽

De Novo ◽

Human Beings ◽

Epigenetic Methylation ◽

Key Enzyme ◽

Dynamics Simulations

The AML-related high-frequent R882H mutation of DNA (cytosine-5)-methyltransferase 3A (DNMT3A), a key enzyme for de novo epigenetic methylation in human beings, was characterized by a disturbing conformation of S-adenosylmethionine (SAM).

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Xrn1p acts at multiple steps in the budding-yeast RNAi pathway to enhance the efficiency of silencing

Nucleic Acids Research ◽

10.1093/nar/gkaa468 ◽

2020 ◽

Author(s):

Matthew A Getz ◽

David E Weinberg ◽

Ines A Drinnenberg ◽

Gerald R Fink ◽

David P Bartel

Keyword(s):

Gene Silencing ◽

Budding Yeast ◽

Genetic Selection ◽

Rnai Pathway ◽

Transcriptional Gene Silencing ◽

Heterochromatin Formation ◽

Post Transcriptional Gene Silencing ◽

Passenger Strand ◽

Transposon Silencing ◽

Target Rna

Abstract RNA interference (RNAi) is a gene-silencing pathway that can play roles in viral defense, transposon silencing, heterochromatin formation and post-transcriptional gene silencing. Although absent from Saccharomyces cerevisiae, RNAi is present in other budding-yeast species, including Naumovozyma castellii, which have an unusual Dicer and a conventional Argonaute that are both required for gene silencing. To identify other factors that act in the budding-yeast pathway, we performed an unbiased genetic selection. This selection identified Xrn1p, the cytoplasmic 5′-to-3′ exoribonuclease, as a cofactor of RNAi in budding yeast. Deletion of XRN1 impaired gene silencing in N. castellii, and this impaired silencing was attributable to multiple functions of Xrn1p, including affecting the composition of siRNA species in the cell, influencing the efficiency of siRNA loading into Argonaute, degradation of cleaved passenger strand and degradation of sliced target RNA.

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Molecular dynamics simulations suggest stabilizing mutations in a de novo designed α/β protein

Protein Engineering Design and Selection ◽

10.1093/protein/gzaa005 ◽

2019 ◽

Vol 32 (7) ◽

pp. 317-329

Author(s):

Matthew Gill ◽

Michelle E McCully

Keyword(s):

Molecular Dynamics ◽

Secondary Structure ◽

Surface Area ◽

De Novo ◽

Md Simulations ◽

Solvent Accessible Surface Area ◽

Hydrophobic Core ◽

Design Strategies ◽

Major Interest ◽

Core Packing

Abstract Designing functional proteins that can withstand extreme heat is beneficial for industrial and protein therapeutic applications. Thus, elucidating the atomic-level determinants of thermostability is a major interest for rational protein design. To that end, we compared the structure and dynamics of a set of previously designed, thermostable proteins based on the activation domain of human procarboxypeptidase A2 (AYEwt). The mutations in these designed proteins were intended to increase hydrophobic core packing and inter-secondary-structure interactions. To evaluate whether these design strategies were successfully deployed, we performed all-atom, explicit-solvent molecular dynamics (MD) simulations of AYEwt and three designed variants at both 25 and 100°C. Our MD simulations agreed with the relative experimental stabilities of the designs based on their secondary structure content, Cα root-mean-square deviation/fluctuation, and buried-residue solvent accessible surface area. Using a contact analysis, we found that the designs stabilize inter-secondary structure interactions and buried hydrophobic surface area, as intended. Based on our analysis, we designed three additional variants to test the role of helix stabilization, core packing, and a Phe → Met mutation on thermostability. We performed the additional MD simulations and analysis on these variants, and these data supported our predictions.

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