HT-SuMD: Making Molecular Dynamics Simulations Suitable for Fragment-Based Screening. a Comparative Study with NMR

<p>In this manuscript, for the first time, we presented a fragment library and we validated its performance by comparison with a well-established technique for fragment screening as solution NMR. We were able to screen 400 different fragments producing a total of 1200 independent fragment-protein recognition pathways. As far as we know, this represents the largest screening based on Molecular dynamics ever reported. Our simulations successfully detected the true binders in the library in a prospective study, showing a notable agreement with a state-of-art screening we performed by NMR on the same dataset.</p>

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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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Absorption of Mechanical Energy via Formation of Ice Nanotubes in Zeolite

Physical Chemistry Chemical Physics ◽

10.1039/d1cp01482j ◽

2021 ◽

Author(s):

Kenji Mochizuki

Keyword(s):

Molecular Dynamics ◽

Molecular Dynamics Simulations ◽

Heterogeneous System ◽

Mechanical Energy ◽

Bulk Water ◽

Pure Silica ◽

Dynamics Simulations ◽

First Time

Abstract Molecular dynamics simulations are carried out for a heterogeneous system composed of bulk water and pure-silica zeolites of the AFI type. Our simulations show, for the first time, the...

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Molecular insight into the Mullins effect: irreversible disentanglement of polymer chains revealed by molecular dynamics simulations

Physical Chemistry Chemical Physics ◽

10.1039/c7cp01142c ◽

2017 ◽

Vol 19 (29) ◽

pp. 19468-19477 ◽

Cited By ~ 11

Author(s):

Chi Ma ◽

Tuo Ji ◽

Christopher G. Robertson ◽

R. Rajeshbabu ◽

Jiahua Zhu ◽

...

Keyword(s):

Molecular Dynamics ◽

Molecular Dynamics Simulations ◽

Molecular Model ◽

Polymer Chains ◽

Mullins Effect ◽

Key Characteristics ◽

Dynamics Simulations ◽

First Time ◽

Insight Into

For the first time, the key characteristics associated with the Mullins effect are captured by a molecular model.

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Intrinsic K-Ras dynamics: A novel molecular dynamics data analysis method shows causality between residue pairs

10.1101/067496 ◽

2016 ◽

Cited By ~ 2

Author(s):

Sezen Vatansever ◽

Zeynep H. Gümüş ◽

Burak Erman

Keyword(s):

Molecular Dynamics ◽

Information Flow ◽

Analysis Method ◽

Future Studies ◽

Correlated Motions ◽

Novel Approach ◽

Decay Times ◽

Dynamics Simulations ◽

First Time ◽

Important Therapeutic Target

SummaryWhile mutant K-Ras is an important therapeutic target for human cancers, there are still no drugs that directly target it. Recent promising studies emphasize the significance of dynamics data to selectively target its active/inactive states. However, despite tremendous information on K-Ras, the direction of information flow in the allosteric regulation of its dynamics has not yet been elucidated. Here, we present a novel approach that identifies causality in correlated motions of proteins and apply it to K-Ras dynamics. Specifically, we analyze molecular dynamics simulations data and comprehensively investigate nucleotide-dependent intrinsic K-Ras activity. We show that GTP binding leads to characteristic residue correlations with relatively long decay times by stabilizing K-Ras motions. Furthermore, we identify for the first time driver-follower relationships of correlated motions in the regulation of K-Ras activity. Our results can be utilized for directly targeting mutant K-Ras in future studies.

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Mechanism of allosteric activation of human mRNA cap methyltransferase (RNMT) by RAM: Insights from accelerated molecular dynamics simulations

10.1101/558502 ◽

2019 ◽

Author(s):

Juan A. Bueren-Calabuig ◽

Marcus Bage ◽

Victoria H. Cowling ◽

Andrei V. Pisliakov

Keyword(s):

Molecular Dynamics ◽

Molecular Dynamics Simulations ◽

Rna Polymerase Ii ◽

Active Site ◽

Allosteric Regulation ◽

Dynamic Network ◽

Binding Model ◽

Accelerated Molecular Dynamics ◽

Dynamics Simulations ◽

First Time

ABSTRACTThe RNA guanine-7 methyltransferase (RNMT) in complex with RNMT-Activating Miniprotein (RAM) catalyses the formation of a N7-methylated guanosine cap structure on the 5’ end of nascent RNA polymerase II transcripts. The mRNA cap protects the transcript from exonucleases and recruits cap-binding complexes that mediate RNA processing, export and translation. By using microsecond standard and accelerated molecular dynamics simulations, we provide for the first time a detailed molecular mechanism of allosteric regulation of RNMT by RAM. We show that RAM selects the RNMT active site conformations that are optimal for binding of substrates (AdoMet and the cap), thus enhancing their affinity. Furthermore, our results strongly suggest the likely scenario in which the cap binding promotes the subsequent AdoMet binding, consistent with the previously suggested cooperative binding model. By employing the dynamic network and community analyses, we revealed the underlying long-range allosteric networks and paths that are crucial for allosteric regulation by RAM. Our findings complement and explain previous experimental data on RNMT activity. Moreover, this study provides the most complete description of the cap and AdoMet binding poses and interactions within the enzyme’s active site. This information is critical for the drug discovery efforts that consider RNMT as a promising anti-cancer target.

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Interaction of stable aggregates drives the precipitation of calcium phosphate in supersaturated solutions

CrystEngComm ◽

10.1039/c9ce00658c ◽

2019 ◽

Vol 21 (42) ◽

pp. 6354-6364 ◽

Cited By ~ 5

Author(s):

R. Innocenti Malini ◽

C. L. Freeman ◽

J. H. Harding

Keyword(s):

Molecular Dynamics ◽

Calcium Phosphate ◽

Molecular Dynamics Simulations ◽

Amorphous Calcium Phosphate ◽

Calcium Phosphate Nanoparticles ◽

Dynamics Simulations ◽

First Time ◽

Supersaturated Solutions

Using molecular dynamics simulations, we show for the first time that calcium phosphate nanoparticles of eight formula units are thermodynamically stable and could be key in the nucleation of amorphous calcium phosphate.

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Molecular dynamics simulations of grain boundary diffusion in Al using embedded atom method potentials

Journal of Materials Research ◽

10.1557/jmr.1995.1589 ◽

1995 ◽

Vol 10 (7) ◽

pp. 1589-1592 ◽

Cited By ~ 9

Author(s):

Chun-Li Liu ◽

S.J. Plimpton

Keyword(s):

Molecular Dynamics ◽

Grain Boundary ◽

Boundary Diffusion ◽

Md Simulations ◽

Embedded Atom Method ◽

Melting Temperatures ◽

Embedded Atom ◽

Pair Potentials ◽

Dynamics Simulations ◽

First Time

Molecular dynamics (MD) simulations of diffusion in a Σ5(310) [001] Al tilt grain boundary were performed using for the first time three different potentials based on the embedded atom method (EAM). The EAM potentials that produce more accurate melting temperatures also yield activation energies in better agreement with experimental data. Compared to pair potentials, the EAM potentials also give more accurate results.

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Ab Initio Molecular Dynamics Simulation of Tribochemical Reactions Involving Phosphorus Additives at Sliding Iron Interfaces

10.20944/preprints201803.0265.v1 ◽

2018 ◽

Author(s):

Sophie Loehlé ◽

M. C. Righi

Keyword(s):

Molecular Dynamics ◽

Ab Initio ◽

Dynamics Simulation ◽

Ab Initio Molecular Dynamics ◽

Molecular Dissociation ◽

Iron Phosphide ◽

Dynamics Simulations ◽

Activation Times ◽

First Time ◽

Dissociation Barrier

We performed for the first time to our knowledge fully ab initio molecular dynamics simulations of additive tribochemistry in boundary lubrication conditions. We consider an organophosphourus additive that has been experimentally shown to reduce friction in steel-on-steel sliding contacts thanks to the tribologically-induced formation of an iron phosphide tribofilm. The simulations allow us to observe in real time the molecular dissociation at the sliding iron interface under pressure and to understand the mechanism of iron phosphide formation. We discuss the role played by the mechanical stress by comparing the activation times for molecular dissociation observed in the tribological simulations at different applied loads with that expected on the basis of the dissociation barrier.

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MOLECULAR DYNAMICS SIMULATIONS OF LIQUID CRYSTAL ANCHORING AT AN AMORPHOUS POLYMER SURFACE

International Journal of Modern Physics C ◽

10.1142/s0129183199000310 ◽

1999 ◽

Vol 10 (02n03) ◽

pp. 415-429 ◽

Cited By ~ 8

Author(s):

T. P. DOERR ◽

P. L. TAYLOR

Keyword(s):

Molecular Dynamics ◽

Liquid Crystal ◽

Force Field ◽

Molecular Dynamics Simulations ◽

Amorphous Polymer ◽

Polymer Surface ◽

The Other ◽

Substantial Fraction ◽

Dynamics Simulations ◽

First Time

Atomistic molecular dynamics simulations have been used, apparently for the first time, to investigate the anchoring behavior of a liquid crystal at the interface with an amorphous polymer. The simulations studied a system consisting of the nematogen 5CB at the surface of amorphous polyethylene, and used the simple Dreiding II force field. The simulations indicate a preference for nonplanar anchoring. Two distinct microscopic paths have been identified by which the liquid crystal changes orientation at the surface. In one case, only one or a few of the 5CB molecules are rotating at any particular time. In the other case, a substantial fraction of the molecules rotate simultaneously.

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