Revealing Topological Barriers against Knot Untying in Thermal and Mechanical Protein Unfolding by Molecular Dynamics Simulations

The knot is one of the most remarkable topological features identified in an increasing number of proteins with important functions. However, little is known about how the knot is formed during protein folding, and untied or maintained in protein unfolding. By means of all-atom molecular dynamics simulation, here we employ methyltransferase YbeA as the knotted protein model to analyze changes of the knotted conformation coupled with protein unfolding under thermal and mechanical denaturing conditions. Our results show that the trefoil knot in YbeA is occasionally untied via knot loosening rather than sliding under enhanced thermal fluctuations. Through correlating protein unfolding with changes in the knot position and size, several aspects of barriers that jointly suppress knot untying are revealed. In particular, protein unfolding is always prior to knot untying and starts preferentially from separation of two α-helices (α1 and α5), which protect the hydrophobic core consisting of β-sheets (β1–β4) from exposure to water. These β-sheets form a loop through which α5 is threaded to form the knot. Hydrophobic and hydrogen bonding interactions inside the core stabilize the loop against loosening. In addition, residues at N-terminal of α5 define a rigid turning to impede α5 from sliding out of the loop. Site mutations are designed to specifically eliminate these barriers, and easier knot untying is achieved under the same denaturing conditions. These results provide new molecular level insights into the folding/unfolding of knotted proteins.

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Multicanonical Molecular Dynamics Simulation Study of the Liquid-Solid and Solid-Solid Transitions in Lennard-Jones Clusters

ASME/JSME 2011 8th Thermal Engineering Joint Conference ◽

10.1115/ajtec2011-44457 ◽

2011 ◽

Author(s):

Toshihiro Kaneko ◽

Kenji Yasuoka ◽

Ayori Mitsutake ◽

Xiao Cheng Zeng

Keyword(s):

Molecular Dynamics ◽

Heat Capacity ◽

Transition Temperature ◽

Peak Position ◽

Temperature Curve ◽

Dynamics Simulation ◽

Lennard Jones ◽

Dynamics Simulations ◽

First Time ◽

Good Agreement

Multicanonical molecular dynamics simulations are applied, for the first time, to study the liquid-solid and solid-solid transitions in Lennard-Jones (LJ) clusters. The transition temperatures are estimated based on the peak position in the heat capacity versus temperature curve. For LJ31, LJ58 and LJ98, our results on the solid-solid transition temperature are in good agreement with previous ones. For LJ309, the predicted liquid-solid transition temperature is also in agreement with previous result.

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Reactive molecular dynamics simulation of the high-temperature pyrolysis of 2,2′,2′′,4,4′,4′′,6,6′,6′′-nonanitro-1,1′:3′,1′′-terphenyl (NONA)

RSC Advances ◽

10.1039/c9ra10261b ◽

2020 ◽

Vol 10 (9) ◽

pp. 5507-5515

Author(s):

Liang Song ◽

Feng-Qi Zhao ◽

Si-Yu Xu ◽

Xue-Hai Ju

Keyword(s):

Molecular Dynamics ◽

High Temperature ◽

Molecular Dynamics Simulation ◽

Molecular Dynamics Simulations ◽

Dynamics Simulation ◽

Reactive Molecular Dynamics ◽

Ring Compounds ◽

Fused Ring ◽

Dynamics Simulations

The bimolecular and fused ring compounds are found in the high-temperature pyrolysis of NONA using ReaxFF molecular dynamics simulations.

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Folding and Intrinsic Disorder of the Receptor Tyrosine Kinase KIT Insert Domain Seen by Conventional Molecular Dynamics Simulations

International Journal of Molecular Sciences ◽

10.3390/ijms22147375 ◽

2021 ◽

Vol 22 (14) ◽

pp. 7375

Author(s):

Julie Ledoux ◽

Alain Trouvé ◽

Luba Tchertanov

Keyword(s):

Molecular Dynamics ◽

Molecular Dynamics Simulations ◽

Tertiary Structure ◽

Average Distance ◽

Intrinsic Disorder ◽

Accessible Surface Area ◽

Solvent Accessible Surface Area ◽

Hydrophobic Core ◽

Direct Evaluation ◽

Dynamics Simulations

The kinase insert domain (KID) of RTK KIT is the key recruitment region for downstream signalling proteins. KID, studied by molecular dynamics simulations as a cleaved polypeptide and as a native domain fused to KIT, showed intrinsic disorder represented by a set of heterogeneous conformations. The accurate atomistic models showed that the helical fold of KID is mainly sequence dependent. However, the reduced fold of the native KID suggests that its folding is allosterically controlled by the kinase domain. The tertiary structure of KID represents a compact array of highly variable α- and 310-helices linked by flexible loops playing a principal role in the conformational diversity. The helically folded KID retains a collapsed globule-like shape due to non-covalent interactions associated in a ternary hydrophobic core. The free energy landscapes constructed from first principles—the size, the measure of the average distance between the conformations, the amount of helices and the solvent-accessible surface area—describe the KID disorder through a collection of minima (wells), providing a direct evaluation of conformational ensembles. We found that the cleaved KID simulated with restricted N- and C-ends better reproduces the native KID than the isolated polypeptide. We suggest that a cyclic, generic KID would be best suited for future studies of KID f post-transduction effects.

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Protein unfolding by SDS: the microscopic mechanisms and the properties of the SDS-protein assembly

Nanoscale ◽

10.1039/c9nr09135a ◽

2020 ◽

Vol 12 (9) ◽

pp. 5422-5434 ◽

Cited By ~ 1

Author(s):

David Winogradoff ◽

Shalini John ◽

Aleksei Aksimentiev

Keyword(s):

Molecular Dynamics ◽

Molecular Dynamics Simulations ◽

Anionic Surfactant ◽

Protein Unfolding ◽

Protein Assembly ◽

Full Length ◽

Dynamics Simulations

Molecular dynamics simulations reveal how anionic surfactant SDS and heat unfold full-length proteins.

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Molecular Dynamics Simulation Study of Lecithin Inhibiting Hydrate-Dissociation

Materials Science Forum ◽

10.4028/www.scientific.net/msf.890.252 ◽

2017 ◽

Vol 890 ◽

pp. 252-259

Author(s):

Le Wang ◽

Guan Cheng Jiang ◽

Xin Lin ◽

Xian Min Zhang ◽

Qi Hui Jiang

Keyword(s):

Molecular Dynamics ◽

Water Movement ◽

Simulation Analysis ◽

Mass Density ◽

Dynamics Simulation ◽

Dissociation Process ◽

Hydrate Dissociation ◽

Hydrocarbon Chains ◽

Dynamics Simulations ◽

Mass Density Profile

Molecular dynamics simulations are used to study the dissociation inhibiting mechanism of lecithin for structure I hydrates. Adsorption characteristics of lecithin and PVP (poly (N-vinylpyrrolidine)) on the hydrate surfaces were performed in the NVT ensemble at temperatures of 277K and the hydrate dissociation process were simulated in the NPT ensemble at same temperature. The results show that hydrate surfaces with lecithin is more stable than the ones with PVP for the lower potential energy. The conformation of lecithin changes constantly after the balanced state is reached while the PVP molecular dose not. Lecithin molecule has interaction with lecithin nearby and hydrocarbon-chains of lecithin molecules will form a network to prevent the diffusion of water and methane molecules, which will narrow the available space for hydrate methane and water movement. Compared with PVP-hydrate simulation, analysis results (snapshots and mass density profile) of the dissociation simulations show that lecithin-hydrate dissociates more slowly.

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Molecular Dynamics Simulations of High Energy Cascades in Iron

MRS Proceedings ◽

10.1557/proc-373-21 ◽

1994 ◽

Vol 373 ◽

Cited By ~ 9

Author(s):

Roger E. Stoller

Keyword(s):

Molecular Dynamics ◽

Three Dimensional ◽

High Energy ◽

Dynamics Simulation ◽

Method Of Molecular Dynamics ◽

Energy Cascades ◽

Iron Based ◽

The Many ◽

Property Changes ◽

Dynamics Simulations

AbstractA series of high-energy, up to 20 keV, displacement cascades in iron have been investigated for times up to 200 ps at 100 K using the method of molecular dynamics simulation. Thesimulations were carried out using the MOLDY code and a modified version of the many-bodyinteratomic potential developed by Finnis and Sinclair. The paper focuses on those results obtained at the highest energies, 10 and 20 keV. The results indicate that the fraction of the Frenkel pairs surviving in-cascade recombination remains fairly high in iron and that the fraction of the surviving point defects that cluster is lower than in materials such as copper. In particular, vacancy clustering appears to be inhibited in iron. Some of the interstitial clusters were observed to exhibit an unexpectedly complex, three-dimensional morphology. The observations are discussed in terms of their relevance to microstructural evolution and mechanical property changes in irradiated iron-based alloys.

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Molecular Dynamics Simulation of Sputtering with Mmany-Body Interactions

MRS Proceedings ◽

10.1557/proc-100-145 ◽

1988 ◽

Vol 100 ◽

Author(s):

Davy Y. Lo ◽

Tom A. Tombrello ◽

Mark H. Shapiro ◽

Don E. Harrison

Keyword(s):

Molecular Dynamics ◽

Molecular Dynamics Simulation ◽

Single Crystal ◽

Low Energy ◽

Dynamics Simulation ◽

Embedded Atom Method ◽

Many Body ◽

Embedded Atom ◽

Dynamics Simulations ◽

Small Single Crystal

ABSTRACTMany-body forces obtained by the Embedded-Atom Method (EAM) [41 are incorporated into the description of low energy collisions and surface ejection processes in molecular dynamics simulations of sputtering from metal targets. Bombardments of small, single crystal Cu targets (400–500 atoms) in three different orientations ({100}, {110}, {111}) by 5 keV Ar+ ions have been simulated. The results are compared to simulations using purely pair-wise additive interactions. Significant differences in the spectra of ejected atoms are found.

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Molecular Dynamics Simulation of Wetting Behavior: Contact Angle Dependency on Water Potential Models

ICS Physical Chemistry ◽

10.34311/icspc.2021.1.1.10 ◽

2021 ◽

Vol 1 (1) ◽

pp. 10

Author(s):

Lukman Hakim ◽

Irsandi Dwi Oka Kurniawan ◽

Ellya Indahyanti ◽

Irwansyah Putra Pradana

Keyword(s):

Molecular Dynamics ◽

Contact Angle ◽

Liquid Droplet ◽

Center Of Mass ◽

Contact Angles ◽

Surface Wettability ◽

Dynamics Simulation ◽

Potential Models ◽

Surface Hydrophilicity ◽

Dynamics Simulations

The underlying principle of surface wettability has obtained great attentions for the development of novel functional surfaces. Molecular dynamics simulations has been widely utilized to obtain molecular-level details of surface wettability that is commonly quantified in term of contact angle of a liquid droplet on the surface. In this work, the sensitivity of contact angle calculation at various degrees of surface hydrophilicity to the adopted potential models of water: SPC/E, TIP4P, and TIP5P, is investigated. The simulation cell consists of a water droplet on a structureless surface whose hydrophilicity is modified by introducing a scaling factor to the water-surface interaction parameter. The simulation shows that the differences in contact angle described by the potential models are systematic and become more visible with the increase of the surface hydrophilicity. An alternative method to compute a contact angle based on the height of center-of-mass of the droplet is also evaluated, and the resulting contact angles are generally larger than those determined from the liquid-gas interfacial line.

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