Unraveling cGAS catalytic mechanism upon DNA activation through molecular dynamics simulations

2021 ◽  
Author(s):  
Jordi Soler ◽  
Pedro Paiva ◽  
Maria Joao Joao Ramos ◽  
Pedro Alexandrino Fernandes ◽  
Marie Brut
Keyword(s):  
Molecular Dynamics ◽  
Dna Binding ◽  
Molecular Dynamics Simulations ◽  
Cyclic Gmp ◽  
Catalytic Mechanism ◽  
System P ◽  
Dynamics Simulations ◽  
Cyclic Dinucleotide

Cyclic GMP-AMP Synthase (cGAS) is activated upon DNA binding and catalyzes the synthesis of 2’,3’-cGAMP from GTP and ATP. This cyclic dinucleotide is a messenger that triggers the autoimmune system...

Thermal boundary conductance between Al films and GaN nanowires investigated with molecular dynamics

2014 ◽  
Vol 16 (20) ◽  
pp. 9403-9410 ◽  
Author(s):  
Xiao-wang Zhou ◽  
Reese E. Jones ◽  
Patrick E. Hopkins ◽  
Thomas E. Beechem
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Thermal Transport ◽  
Thermal Boundary Conductance ◽  
Gan Nanowires ◽  
System P ◽  
Dynamics Simulations ◽  
Important System

Using molecular dynamics simulations, we studied the thermal boundary conductance between GaN nanowires and Al films and showed how it may be possible to enhance interfacial thermal transport in this important system.

scholarly journals Probing the Relationship between Anti-Pneumocystis carinii Activity and DNA Binding of Bisamidines by Molecular Dynamics Simulations

Molecules ◽  
2015 ◽  
Vol 20 (4) ◽  
pp. 5942-5964 ◽  
Author(s):  
Teresa Żołek ◽  
Dorota Maciejewska ◽  
Jerzy Żabiński ◽  
Paweł Kaźmierczak ◽  
Mateusz Rezler
Keyword(s):  
Molecular Dynamics ◽  
Dna Binding ◽  
Molecular Dynamics Simulations ◽  
Pneumocystis Carinii ◽  
Dynamics Simulations ◽  
The Relationship

scholarly journals ExaViz: a flexible framework to analyse, steer and interact with molecular dynamics simulations

2014 ◽  
Vol 169 ◽  
pp. 119-142 ◽  
Author(s):  
Matthieu Dreher ◽  
Jessica Prevoteau-Jonquet ◽  
Mikael Trellet ◽  
Marc Piuzzi ◽  
Marc Baaden ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Molecular System ◽  
Data Set ◽  
System P ◽  
Alternative Approach ◽  
Long Time ◽  
Flexible Framework ◽  
Sheer Size ◽  
Dynamics Simulations

The amount of data generated by molecular dynamics simulations of large molecular assemblies and the sheer size and complexity of the systems studied call for new ways to analyse, steer and interact with such calculations. Traditionally, the analysis is performed off-line once the huge amount of simulation results have been saved to disks, thereby stressing the supercomputer I/O systems, and making it increasingly difficult to handle post-processing and analysis from the scientist's office. The ExaViz framework is an alternative approach developed to couple the simulation with analysis tools to process the data as close as possible to their source of creation, saving a reduced, more manageable and pre-processed data set to disk. ExaViz supports a large variety of analysis and steering scenarios. Our framework can be used for live sessions (simulations short enough to be fully followed by the user) as well as batch sessions (long-time batch executions). During interactive sessions, at runtime, the user can display plots from analysis, visualise the molecular system and steer the simulation with a haptic device. We also emphasise how a CAVE-like immersive environment could be used to leverage such simulations, offering a large display surface to view and intuitively navigate the molecular system.

A study on the structural features of SELK, an over-expressed protein in hepatocellular carcinoma, by molecular dynamics simulations in a lipid–water system

2016 ◽  
Vol 12 (10) ◽  
pp. 3209-3222 ◽  
Author(s):  
Andrea Polo ◽  
Stefano Guariniello ◽  
Giovanni Colonna ◽  
Gennaro Ciliberto ◽  
Susan Costantini
Keyword(s):  
Hepatocellular Carcinoma ◽  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Conformational Dynamics ◽  
Water System ◽  
Structural Features ◽  
System P ◽  
Dynamics Simulations

Terminal regions in SELK present different conformational dynamics being coupled complicatedly through the membrane.

scholarly journals Somatic mutations in CTCF zinc fingers produce cellular phenotypes explained by structure-function relationships

2021 ◽  
Author(s):  
John EJ Rasko ◽  
Charles Geoffrey Bailey ◽  
Shailendra Gupta ◽  
Cynthia Metierre ◽  
Punkaja Amarasekera ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Cell Growth ◽  
Dna Binding ◽  
Structure Function ◽  
Molecular Dynamics Simulations ◽  
Zinc Fingers ◽  
Cancer Genome ◽  
Tumour Suppressor ◽  
Dynamics Simulations ◽  
Cellular Phenotypes

Background: Human cancers commonly contain mutations in transcription factors that lead to aberrant DNA binding or altered effector function at target sites. One such factor significantly mutated in cancer is the evolutionarily-conserved CCCTC-binding factor (CTCF), which has fundamental roles in maintaining chromatin architecture and transcriptional regulation. Numerous cancer genome sequencing and functional studies have revealed CTCF's role as a haploinsufficient tumour suppressor gene. However, to date, structure-function relationships of somatic CTCF mutations have not been examined. Methods: We collated somatic CTCF mutations from cancer genome portals and published studies to determine their nature, frequency, distribution and potential functional impact. We undertook an in-depth examination of 5 CTCF missense zinc finger (ZF) mutations occurring within key intra- and inter-ZF residues. We performed functional analyses including cell growth, colony-formation, chromatin immunoprecipitation and transcriptional reporter assays. Based on their homology, each ZF mutation was then modelled on CTCF's ZF domain crystal structure and its structural impact analysed using molecular dynamics simulations. Results: We observed an enrichment of somatic missense mutations occurring in the ZF region of CTCF, compared to the unstructured N- and C-termini. Functional characterisation of CTCF ZF mutations revealed a complete (L309P, R339W, R377H) or intermediate (R339Q) abrogation as well as an enhancement (G420D) of the anti-proliferative effects of CTCF. DNA binding at select sites was disrupted and transcriptional regulatory activities abrogated. In silico mutagenesis revealed that L309P had the highest mutation energy and thus most severe impact on protein stability. Molecular docking and molecular dynamics simulations confirmed that mutations in residues specifically contacting DNA bases or backbone exhibited loss of DNA binding (R339Q, R339W, R377H). Remarkably, R339Q and G420D were stabilised by the formation of new primary DNA bonds. All mutations exhibited some loss or gain of bonds at neighbouring residues, often in adjacent zinc fingers. Conclusions: Our data confirm the significant negative impact haploinsufficient CTCF ZF mutations have on its tumour suppressor function. A spectrum of loss-, change- and gain-of-function impacts in CTCF zinc fingers are observed in cell growth regulation and gene regulatory activities. We have established that diverse cellular phenotypes in CTCF are explained by examining structure-function relationships.

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