scholarly journals Global and local mechanical properties control endonuclease reactivity of a DNA origami nanostructure

2020 ◽  
Vol 48 (9) ◽  
pp. 4672-4680 ◽  
Author(s):  
Antonio Suma ◽  
Alex Stopar ◽  
Allen W Nicholson ◽  
Matteo Castronovo ◽  
Vincenzo Carnevale
Keyword(s):  
Mechanical Properties ◽  
Dna Origami ◽  
Coarse Grained ◽  
Free Energy Barrier ◽  
Stable Conformation ◽  
Rational Engineering ◽  
Dynamics Simulations ◽  
Global Fluctuations ◽  
Global And Local ◽  
Good Agreement

Abstract We used coarse-grained molecular dynamics simulations to characterize the global and local mechanical properties of a DNA origami triangle nanostructure. The structure presents two metastable conformations separated by a free energy barrier that is lowered upon omission of four specific DNA staples (defect). In contrast, only one stable conformation is present upon removing eight staples. The metastability is explained in terms of the intrinsic conformations of the three trapezoidal substructures. We computationally modeled the local accessibility to endonucleases, to predict the reactivity of twenty sites, and found good agreement with the experimental data. We showed that global fluctuations affect local reactivity: the removal of the DNA staples increased the computed accessibility to a restriction enzyme, at sites as distant as 40 nm, due to an increase in global fluctuation. These results raise the intriguing possibility of the rational engineering of allosterically modulated DNA origami.

scholarly journals Global and local mechanical properties control endonuclease reactivity of a DNA origami nanostructure

2019 ◽  
Author(s):  
Antonio Suma ◽  
Alex Stopar ◽  
Allen W. Nicholson ◽  
Matteo Castronovo ◽  
Vincenzo Carnevale
Keyword(s):  
Mechanical Properties ◽  
Dna Origami ◽  
Coarse Grained ◽  
Free Energy Barrier ◽  
Stable Conformation ◽  
Rational Engineering ◽  
Dynamics Simulations ◽  
Global Fluctuations ◽  
Global And Local ◽  
Good Agreement

ABSTRACTWe used coarse-grained molecular dynamics simulations to characterize the global and local mechanical properties of a DNA origami triangle nanostructure. The structure presents two metastable conformations separated by a free energy barrier that is lowered upon omission of four specific DNA staples (defect). In contrast, only one stable conformation is present upon removing eight staples. The metastability is explained in terms of the intrinsic conformations of the three trapezoidal substructures. We computationally modeled the local accessibility to endonucleases, to predict the reactivity of twenty sites, and found good agreement with the experimental data. We showed that global fluctuations affect local reactivity: the removal of the DNA staples increased the computed accessibility to a restriction enzyme, at sites as distant as 40nm, due to an increase in global fluctuation. These results raise the intriguing possibility of the rational engineering of allosterically modulated DNA origami.

scholarly journals On the folding of a structurally complex protein to its metastable active state

2018 ◽  
Vol 115 (9) ◽  
pp. 1998-2003 ◽  
Author(s):  
V. V. Hemanth Giri Rao ◽  
Shachi Gosavi
Keyword(s):  
Free Energy ◽  
Energy Barrier ◽  
Coarse Grained ◽  
Structural Basis ◽  
Free Energy Barrier ◽  
Active Conformation ◽  
Protease Inhibition ◽  
Stable Conformation ◽  
Folding Simulations ◽  
And Function

For successful protease inhibition, the reactive center loop (RCL) of the two-domain serine protease inhibitor, α1-antitrypsin (α1-AT), needs to remain exposed in a metastable active conformation. The α1-AT RCL is sequestered in a β-sheet in the stable latent conformation. Thus, to be functional, α1-AT must always fold to a metastable conformation while avoiding folding to a stable conformation. We explore the structural basis of this choice using folding simulations of coarse-grained structure-based models of the two α1-AT conformations. Our simulations capture the key features of folding experiments performed on both conformations. The simulations also show that the free energy barrier to fold to the latent conformation is much larger than the barrier to fold to the active conformation. An entropically stabilized on-pathway intermediate lowers the barrier for folding to the active conformation. In this intermediate, the RCL is in an exposed configuration, and only one of the two α1-AT domains is folded. In contrast, early conversion of the RCL into a β-strand increases the coupling between the two α1-AT domains in the transition state and creates a larger barrier for folding to the latent conformation. Thus, unlike what happens in several proteins, where separate regions promote folding and function, the structure of the RCL, formed early during folding, determines both the conformational and the functional fate of α1-AT. Further, the short 12-residue RCL modulates the free energy barrier and the folding cooperativity of the large 370-residue α1-AT. Finally, we suggest experiments to test the predicted folding mechanism for the latent state.

scholarly journals Mechanical anisotropy of two-dimensional metamaterials: a computational study

2019 ◽  
Vol 1 (8) ◽  
pp. 2891-2900 ◽  
Author(s):  
Ning Liu ◽  
Mathew Becton ◽  
Liuyang Zhang ◽  
Keke Tang ◽  
Xianqiao Wang
Keyword(s):  
Mechanical Properties ◽  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Computational Study ◽  
2D Materials ◽  
Mechanical Anisotropy ◽  
Coarse Grained ◽  
Two Dimensional ◽  
Geometrical Factors ◽  
Dynamics Simulations

Mechanical properties, especially negative Poisson's, of 2D sinusoidal lattice metamaterials based on 2D materials depends highly on both geometrical factors and tuned mechanical anisotropy according to our generic coarse-grained molecular dynamics simulations.

MOLECULAR DYNAMICS SIMULATIONS OF FURAN RESIN (POLYFURFURYL ALCOHOL): PREDICTING MECHANICAL PROPERTIES

2021 ◽  
Author(s):  
JOSH KEMPPAINEN ◽  
IVAN GALLEGOS ◽  
PRATHAMESH DESHPANDE ◽  
JACOB GISSINGER ◽  
GREGORY ODEGARD
Keyword(s):  
Mechanical Properties ◽  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Acid Corrosion ◽  
Carbon Composites ◽  
Corrosion Resistant ◽  
Polyfurfuryl Alcohol ◽  
Furan Resin ◽  
Dynamics Simulations ◽  
Good Agreement

Furan resins can be used as precursor resin for Carbon-Carbon Composites but has also been used in adhesives, acid/corrosion resistant materials, and as an alternative fuel precursor [15]. This paper contains the most current understanding of the structure of furan resin and a Molecular Dynamics workflow for computationally simulating its polymerization with the 'fix bond/react' command implemented in LAMMPS. The predicted mechanical properties of the polymerized resin are in good agreement with the literature values.

Coarse-grained simulation: a high-throughput computational approach to membrane proteins

2008 ◽  
Vol 36 (1) ◽  
pp. 27-32 ◽  
Author(s):  
Mark S.P. Sansom ◽  
Kathryn A. Scott ◽  
Peter J. Bond
Keyword(s):  
Membrane Proteins ◽  
Lipid Bilayer ◽  
High Throughput ◽  
Protein Interactions ◽  
Coarse Grained ◽  
Atomistic Simulations ◽  
Lactose Permease ◽  
Coarse Grained Simulations ◽  
Dynamics Simulations ◽  
Good Agreement

An understanding of the interactions of membrane proteins with a lipid bilayer environment is central to relating their structure to their function and stability. A high-throughput approach to prediction of membrane protein interactions with a lipid bilayer based on coarse-grained Molecular Dynamics simulations is described. This method has been used to develop a database of CG simulations (coarse-grained simulations) of membrane proteins (http://sbcb.bioch.ox.ac.uk/cgdb). Comparison of CG simulations and AT simulations (atomistic simulations) of lactose permease reveals good agreement between the two methods in terms of predicted lipid headgroup contacts. Both CG and AT simulations predict considerable local bilayer deformation by the voltage sensor domain of the potassium channel KvAP.

scholarly journals Analysis on Microstructure–Property Linkages of Filled Rubber Using Machine Learning and Molecular Dynamics Simulations

Polymers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 2683
Author(s):  
Takashi Kojima ◽  
Takashi Washio ◽  
Satoshi Hara ◽  
Masataka Koishi ◽  
Naoya Amino
Keyword(s):  
Machine Learning ◽  
Mechanical Properties ◽  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
High Stress ◽  
Classification Model ◽  
Machine Learning Techniques ◽  
Coarse Grained ◽  
Filled Rubber ◽  
Dynamics Simulations

A better understanding of the microstructure–property relationship can be achieved by sampling and analyzing a microstructure leading to a desired material property. During the simulation of filled rubber, this approach includes extracting common aggregates from a complex filler morphology consisting of hundreds of filler particles. However, a method for extracting a core structure that determines the rubber mechanical properties has not been established yet. In this study, we analyzed complex filler morphologies that generated extremely high stress using two machine learning techniques. First, filler morphology was quantified by persistent homology and then vectorized using persistence image as the input data. After that, a binary classification model involving logistic regression analysis was developed by training a dataset consisting of the vectorized morphology and stress-based class. The filler aggregates contributing to the desired mechanical properties were extracted based on the trained regression coefficients. Second, a convolutional neural network was employed to establish a classification model by training a dataset containing the imaged filler morphology and class. The aggregates strongly contributing to stress generation were extracted by a kernel. The aggregates extracted by both models were compared, and their shapes and distributions producing high stress levels were discussed. Finally, we confirmed the effects of the extracted aggregates on the mechanical property, namely the validity of the proposed method for extracting stress-contributing fillers, by performing coarse-grained molecular dynamics simulations.

scholarly journals Tailoring the mechanical properties of polymer nanocomposites via interfacial engineering

2019 ◽  
Vol 21 (34) ◽  
pp. 18714-18726 ◽  
Author(s):  
Naishen Gao ◽  
Guanyi Hou ◽  
Jun Liu ◽  
Jianxiang Shen ◽  
Yangyang Gao ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Polymer Nanocomposites ◽  
Coarse Grained ◽  
Enhancement Effect ◽  
Interfacial Engineering ◽  
Dynamics Simulations ◽  
Coarse Grained Molecular Dynamics

Using coarse-grained molecular-dynamics simulations, we have successfully fabricated ideal, mechanically-interlocked polymer nanocomposites exhibiting a significant mechanical enhancement effect.

Cofilin reduces the mechanical properties of actin filaments: approach with coarse-grained methods

2015 ◽  
Vol 17 (12) ◽  
pp. 8148-8158 ◽  
Author(s):  
Jae In Kim ◽  
Junpyo Kwon ◽  
Inchul Baek ◽  
Harold S. Park ◽  
Sungsoo Na
Keyword(s):  
Mechanical Properties ◽  
Normal Mode Analysis ◽  
Beam Theory ◽  
Dynamics Simulation ◽  
Coarse Grained ◽  
Mode Analysis ◽  
Elastic Network Model ◽  
Elastic Network ◽  
Good Agreement ◽  
The Continuum

We applied a coarse-grained molecular dynamics simulation (CGMD) method and constructed elastic network model-based structures, actin and cofilactin filaments. Based on a normal mode analysis, the continuum beam theory was used to calculate the mechanical properties and the results showed good agreement with the established experimental data.

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