Mechanical Unfolding of Proteins—A Comparative Nonequilibrium Molecular Dynamics Study

Mykuliak, Vasyl V.; Sikora, Mateusz; Booth, Jonathan J.; Cieplak, Marek; Shalashilin, Dmitrii V.; Hytönen, Vesa P.

doi:10.1016/j.bpj.2020.07.030

Cited by 8 publications

(6 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A brief discussion of the basic principles, recent advances, and limitations seems warranted to discuss the relevance of this approach to cell function. See, e.g., [8] for a technical description of Gromacs, a freely available MD software providing a good example of currently performed MD simulations [9,10].…”

Section: The Initial Choice Of Parameters Used To Describe Cell Prope...mentioning

confidence: 99%

Is There a Need for a More Precise Description of Biomolecule Interactions to Understand Cell Function?

Bongrand

2022

CIMB

View full text Add to dashboard Cite

An important goal of biological research is to explain and hopefully predict cell behavior from the molecular properties of cellular components. Accordingly, much work was done to build extensive “omic” datasets and develop theoretical methods, including computer simulation and network analysis to process as quantitatively as possible the parameters contained in these resources. Furthermore, substantial effort was made to standardize data presentation and make experimental results accessible to data scientists. However, the power and complexity of current experimental and theoretical tools make it more and more difficult to assess the capacity of gathered parameters to support optimal progress in our understanding of cell function. The purpose of this review is to focus on biomolecule interactions, the interactome, as a specific and important example, and examine the limitations of the explanatory and predictive power of parameters that are considered as suitable descriptors of molecular interactions. Recent experimental studies on important cell functions, such as adhesion and processing of environmental cues for decision-making, support the suggestion that it should be rewarding to complement standard binding properties such as affinity and kinetic constants, or even force dependence, with less frequently used parameters such as conformational flexibility or size of binding molecules.

show abstract

Section: The Initial Choice Of Parameters Used To Describe Cell Prope...mentioning

confidence: 99%

Is There a Need for a More Precise Description of Biomolecule Interactions to Understand Cell Function?

Bongrand

2022

CIMB

View full text Add to dashboard Cite

show abstract

“…4 k B is Boltzmann's constant and T is the absolute temperature. 5 Note however that some shortcuts such as 'steered molecular dynamics' or 'umbrella sampling' are still needed to achieve this goal [145,146]. 6 The wall shear rate G is the velocity gradient: according to basic principles of fluid mechanics, the fluid velocity at a low distance z from the blood wall is approximately equal to the product Gz.…”

Section: Endnotesmentioning

confidence: 99%

“…The outstanding advances of molecular dynamics and the so-called artificial intelligence [ 145 , 146 ] exemplify the power of computer simulation in life sciences. It is now feasible to predict the behaviour of a protein by simulating the dynamics of as much as 100 000 atoms during periods of time sufficiently long to mimic folding and ligand–receptor association.…”

Section: The Road Aheadmentioning

confidence: 99%

See 1 more Smart Citation

Mechanotransduction as a major driver of cell behaviour: mechanisms, and relevance to cell organization and future research

Puech

Bongrand

2021

Open Biol.

View full text Add to dashboard Cite

How do cells process environmental cues to make decisions? This simple question is still generating much experimental and theoretical work, at the border of physics, chemistry and biology, with strong implications in medicine. The purpose of mechanobiology is to understand how biochemical and physical cues are turned into signals through mechanotransduction. Here, we review recent evidence showing that (i) mechanotransduction plays a major role in triggering signalling cascades following cell–neighbourhood interaction; (ii) the cell capacity to continually generate forces, and biomolecule properties to undergo conformational changes in response to piconewton forces, provide a molecular basis for understanding mechanotransduction; and (iii) mechanotransduction shapes the guidance cues retrieved by living cells and the information flow they generate. This includes the temporal and spatial properties of intracellular signalling cascades. In conclusion, it is suggested that the described concepts may provide guidelines to define experimentally accessible parameters to describe cell structure and dynamics, as a prerequisite to take advantage of recent progress in high-throughput data gathering, computer simulation and artificial intelligence, in order to build a workable, hopefully predictive, account of cell signalling networks.

show abstract

“…In addition, molecular dynamics simulations have difficulty calculating inter-protein forces and have only been able to modelled talin unfolding at supra-physiological forces. Previous all-atom and coarse-grained simulations of talin’s rod domain 20 , 21 , 23 , 24 , have stretched a section of talin’s rod domain by applying a constant velocity of to one of the two terminal ends of the sub-domain. In these simulations, peak force values across an alpha-helix bundle can range from 400 to 1500 pN.…”

Section: Introductionmentioning

confidence: 99%

An efficient alpha helix model and simulation framework for stationary electrostatic interaction force estimation

Butcher

Harwin

Jones

2021

Sci Rep

View full text Add to dashboard Cite

The alpha-helix coiled-coils within talin’s rod domain have mechanical and signalling functions through their unfolding and refolding dynamics. A better understanding of talin unfolding events and the forces that are involved should allow better prediction of talin signalling. To overcome the current limitations of force measuring in molecular dynamics simulations, a new simulation framework was developed which operated directly within the force domain. Along with a corresponding alpha-helix modelling method, the simulation framework was developed drawing on robotic kinematics to specifically target force interactions. Coordinate frames were used efficiently to compartmentalise the simulation structures and static analysis was applied to determine the propagation of forces and torques through the protein structure. The results of the electrostatic approximation using Coulomb’s law shows a simulated force interaction within the physiological relevant range of 5–40 pN for the rod sub-domains of talin. This covers the range of forces talin operates in and is 2–3 orders of magnitude closer to experimentally measured values than the compared all-atom and coarse-grained molecular dynamics. This targeted, force-based simulation is, therefore, able to produce more realistic forces values than previous simulation methods.

show abstract

Mechanical Unfolding of Proteins—A Comparative Nonequilibrium Molecular Dynamics Study

Cited by 8 publications

References 44 publications

Is There a Need for a More Precise Description of Biomolecule Interactions to Understand Cell Function?

Is There a Need for a More Precise Description of Biomolecule Interactions to Understand Cell Function?

Mechanotransduction as a major driver of cell behaviour: mechanisms, and relevance to cell organization and future research

An efficient alpha helix model and simulation framework for stationary electrostatic interaction force estimation

Contact Info

Product

Resources

About