A nanoscale reciprocating rotary mechanism with coordinated mobility control

AbstractBiological molecular motors transform chemical energy into mechanical work by coupling cyclic catalytic reactions to large-scale structural transitions. Mechanical deformation can be surprisingly efficient in realizing such coupling, as demonstrated by the F1FO ATP synthase. Here, we describe a synthetic molecular mechanism that transforms a rotary motion of an asymmetric camshaft into reciprocating large-scale transitions in a surrounding stator orchestrated by mechanical deformation. We design the mechanism using DNA origami, characterize its structure via cryo-electron microscopy, and examine its dynamic behavior using single-particle fluorescence microscopy and molecular dynamics simulations. While the camshaft can rotate inside the stator by diffusion, the stator’s mechanics makes the camshaft pause at preferred orientations. By changing the stator’s mechanical stiffness, we accelerate or suppress the Brownian rotation, demonstrating an allosteric coupling between the camshaft and the stator. Our mechanism provides a framework for manufacturing artificial nanomachines that function because of coordinated movements of their components.

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A nanoscale reciprocating rotary mechanism with coordinated mobility control

10.1101/2021.04.27.441587 ◽

2021 ◽

Author(s):

Eva Bertosin ◽

Christopher M. Maffeo ◽

Thomas Drexler ◽

Maximilian N. Honemann ◽

Aleksei Aksimentiev ◽

...

Keyword(s):

Molecular Motors ◽

Large Scale ◽

Mechanical Deformation ◽

Dna Origami ◽

Mobility Control ◽

Rotary Motion ◽

Mechanical Stiffness ◽

Allosteric Coupling ◽

Dynamics Simulations ◽

World Function

AbstractBiological molecular motors transform chemical energy into mechanical work by coupling a cycle of catalytic reactions to large scale structural transitions. Mechanical deformation can be surprisingly efficient in realizing such coupling, as demonstrated by the celebrated example of F1FoATP synthase. Here, we describe a synthetic molecular mechanism that transforms a rotary motion of an asymmetric camshaft into reciprocating large-scale transitions in the structure of the surrounding stator orchestrated by mechanical deformation. We designed the mechanism using DNA origami, characterized the structure of the components and the entire mechanism using cryo-electron microscopy, and examined the mechanism’s dynamic behavior using single-particle fluorescence microscopy and molecular dynamics simulations. The data indicates that, while the camshaft can rotate inside the stator by diffusion, mechanical deformation of the stator makes the camshaft pause at a set of preferred orientations. By changing the mechanical stiffness of the stator, we could accelerate or suppress the Brownian rotation within the mechanism, thereby demonstrating an allosteric coupling between the movement of the camshaft and of the stator, and the ability to tailor the free energy landscape that governs the rotary motion. Our mechanism provides a framework for the manufacture of artificial nanomachines that, just like the man-made machines in the macroscopic world, function because of coordinated movements of their components.

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Allosteric pathway identification through network analysis: from molecular dynamics simulations to interactive 2D and 3D graphs

Faraday Discussions ◽

10.1039/c4fd00024b ◽

2014 ◽

Vol 169 ◽

pp. 303-321 ◽

Cited By ~ 27

Author(s):

Ariane Allain ◽

Isaure Chauvot de Beauchêne ◽

Florent Langenfeld ◽

Yann Guarracino ◽

Elodie Laine ◽

...

Keyword(s):

Molecular Dynamics ◽

Network Analysis ◽

Molecular Dynamics Simulations ◽

Large Scale ◽

Allosteric Regulation ◽

Local Perturbation ◽

Modular Network ◽

Allosteric Coupling ◽

Dynamics Simulations

Allostery is a universal phenomenon that couples the information induced by a local perturbation (effector) in a protein to spatially distant regulated sites. Such an event can be described in terms of a large scale transmission of information (communication) through a dynamic coupling between structurally rigid (minimally frustrated) and plastic (locally frustrated) clusters of residues. To elaborate a rational description of allosteric coupling, we propose an original approach – MOdular NETwork Analysis (MONETA) – based on the analysis of inter-residue dynamical correlations to localize the propagation of both structural and dynamical effects of a perturbation throughout a protein structure. MONETA uses inter-residue cross-correlations and commute times computed from molecular dynamics simulations and a topological description of a protein to build a modular network representation composed of clusters of residues (dynamic segments) linked together by chains of residues (communication pathways). MONETA provides a brand new direct and simple visualization of protein allosteric communication. A GEPHI module implemented in the MONETA package allows the generation of 2D graphs of the communication network. An interactive PyMOL plugin permits drawing of the communication pathways between chosen protein fragments or residues on a 3D representation. MONETA is a powerful tool for on-the-fly display of communication networks in proteins. We applied MONETA for the analysis of communication pathways (i) between the main regulatory fragments of receptors tyrosine kinases (RTKs), KIT and CSF-1R, in the native and mutated states and (ii) in proteins STAT5 (STAT5a and STAT5b) in the phosphorylated and the unphosphorylated forms. The description of the physical support for allosteric coupling by MONETA allowed a comparison of the mechanisms of (a) constitutive activation induced by equivalent mutations in two RTKs and (b) allosteric regulation in the activated and non-activated STAT5 proteins. Our theoretical prediction based on results obtained with MONETA was validated for KIT by in vitro experiments. MONETA is a versatile analytical and visualization tool entirely devoted to the understanding of the functioning/malfunctioning of allosteric regulation in proteins – a crucial basis to guide the discovery of next-generation allosteric drugs.

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Mechanistic analysis of light-driven overcrowded alkene-based molecular motors by multiscale molecular simulations

Physical Chemistry Chemical Physics ◽

10.1039/d0cp06685k ◽

2021 ◽

Vol 23 (14) ◽

pp. 8525-8540

Author(s):

Mudong Feng ◽

Michael K. Gilson

Keyword(s):

Molecular Dynamics ◽

Excited State ◽

Molecular Dynamics Simulations ◽

Ground State ◽

Molecular Motors ◽

Motor Performance ◽

Molecular Simulations ◽

Mechanistic Analysis ◽

Dynamics Simulations ◽

Shed Light

Ground-state and excited-state molecular dynamics simulations shed light on the rotation mechanism of small, light-driven molecular motors and predict motor performance. How fast can they rotate; how much torque and power can they generate?

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Elucidating the Onset of Plasticity in Sliding Contacts Using Differential Computational Orientation Tomography

Tribology Letters ◽

10.1007/s11249-021-01451-9 ◽

2021 ◽

Vol 69 (3) ◽

Author(s):

S. J. Eder ◽

P. G. Grützmacher ◽

M. Rodríguez Ripoll ◽

J. F. Belak

Keyword(s):

Grain Boundary ◽

Large Scale ◽

Surface Deformation ◽

Boundary Migration ◽

Material Design ◽

Lattice Rotation ◽

Time Resolved ◽

Near Surface ◽

Color Saturation ◽

Dynamics Simulations

Abstract Depending on the mechanical and thermal energy introduced to a dry sliding interface, the near-surface regions of the mated bodies may undergo plastic deformation. In this work, we use large-scale molecular dynamics simulations to generate “differential computational orientation tomographs” (dCOT) and thus highlight changes to the microstructure near tribological FCC alloy surfaces, allowing us to detect subtle differences in lattice orientation and small distances in grain boundary migration. The analysis approach compares computationally generated orientation tomographs with their undeformed counterparts via a simple image analysis filter. We use our visualization method to discuss the acting microstructural mechanisms in a load- and time-resolved fashion, focusing on sliding conditions that lead to twinning, partial lattice rotation, and grain boundary-dominated processes. Extracting and laterally averaging the color saturation value of the generated tomographs allows us to produce quantitative time- and depth-resolved maps that give a good overview of the progress and severity of near-surface deformation. Corresponding maps of the lateral standard deviation in the color saturation show evidence of homogenization processes occurring in the tribologically loaded microstructure, frequently leading to the formation of a well-defined separation between deformed and undeformed regions. When integrated into a computational materials engineering framework, our approach could help optimize material design for tribological and other deformation problems. Graphic Abstract .

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Large-Scale Membrane Permeability Prediction of Cyclic Peptides Crossing a Lipid Bilayer Based on Enhanced Sampling Molecular Dynamics Simulations

Journal of Chemical Information and Modeling ◽

10.1021/acs.jcim.1c00380 ◽

2021 ◽

Author(s):

Masatake Sugita ◽

Satoshi Sugiyama ◽

Takuya Fujie ◽

Yasushi Yoshikawa ◽

Keisuke Yanagisawa ◽

...

Keyword(s):

Molecular Dynamics ◽

Molecular Dynamics Simulations ◽

Membrane Permeability ◽

Lipid Bilayer ◽

Cyclic Peptides ◽

Large Scale ◽

Enhanced Sampling ◽

Permeability Prediction ◽

Dynamics Simulations

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Mechanistic Insights from Molecular Dynamics Simulations of Large-Scale Conformational Transitions in the INDY Transport Cycle

Biophysical Journal ◽

10.1016/j.bpj.2020.11.153 ◽

2021 ◽

Vol 120 (3) ◽

pp. 3a-4a

Author(s):

Noah Trebesch ◽

David B. Sauer ◽

Da-Neng Wang ◽

Emad Tajkhorshid

Keyword(s):

Molecular Dynamics ◽

Molecular Dynamics Simulations ◽

Large Scale ◽

Conformational Transitions ◽

Transport Cycle ◽

Dynamics Simulations

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Large-scale molecular dynamics simulations of TiN/TiN(001) epitaxial film growth

Journal of Vacuum Science & Technology A Vacuum Surfaces and Films ◽

10.1116/1.4953404 ◽

2016 ◽

Vol 34 (4) ◽

pp. 041509 ◽

Cited By ~ 19

Author(s):

Daniel Edström ◽

Davide G. Sangiovanni ◽

Lars Hultman ◽

Ivan Petrov ◽

J. E. Greene ◽

...

Keyword(s):

Molecular Dynamics ◽

Molecular Dynamics Simulations ◽

Large Scale ◽

Epitaxial Film ◽

Film Growth ◽

Dynamics Simulations ◽

Epitaxial Film Growth

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Nanoscale Transport Phenomena in PEM of PEFC by Large Scale Molecular Dynamics Simulations

ECS Transactions ◽

10.1149/05002.0859ecst ◽

2013 ◽

Vol 50 (2) ◽

pp. 859-868 ◽

Cited By ~ 2

Author(s):

T. Tokumasu

Keyword(s):

Molecular Dynamics ◽

Molecular Dynamics Simulations ◽

Large Scale ◽

Transport Phenomena ◽

Nanoscale Transport ◽

Dynamics Simulations

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Cooling Process for Directional Solidification in Directed Energy Deposition

Volume 1: Additive Manufacturing; Bio and Sustainable Manufacturing ◽

10.1115/msec2018-6437 ◽

2018 ◽

Author(s):

Keiya Ishiyama ◽

Ryo Koike ◽

Yasuhiro Kakinuma ◽

Tetsuya Suzuki ◽

Takanori Mori

Keyword(s):

Directional Solidification ◽

Thermal Gradient ◽

Large Scale ◽

Energy Deposition ◽

Production Efficiency ◽

Production Costs ◽

Special Structure ◽

Mechanical Stiffness ◽

Directed Energy Deposition ◽

Directed Energy

Additive manufacturing (AM) for metals has attracted attention from industry because of its great potential to enhance production efficiency and reduce production costs. Directed energy deposition (DED) is a metal AM process suitable to produce large-scale freeform metal products. DED entails irradiating the baseplate with a laser beam and launching the metal powder onto the molten spot to produce a metal part on the baseplate. Because the process enables powder from different materials to be used, DED is widely applicable to valuable production work such as for a dissimilar material joint, a graded material, or a part with a special structure. With regard to parts with a special structure, directional solidification can prospectively be used in the power plant and aerospace industries because it can enhance the stiffness in a specific direction via only a simple process. However, conventional approaches for directional solidification require a special mold in order to realize a long-lasting thermal gradient in the part. On the other hand, from the viewpoint of thermal distribution in a produced part, DED is able to control the gradient by controlling the position of the molten pool, i.e., the position of the laser spot. Moreover, unlike casting, the thermal gradient can be precisely oriented in the expected direction, because the laser supplies heat energy on the regulated spot. In this study, the applicability of DED to directional solidification in Inconel® 625 is theoretically and experimentally evaluated through metal structure observation and Vickers hardness measurements. Furthermore, the effect of two different cooling processes on directional solidification is also considered with the aim of improving the mechanical stiffness of a part produced by DED. The observations and experimental results show that both the cooling methods (baseplate cooling and intermittent treatment with coolant) are able to enhance the hardness while retaining the anisotropy.

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