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

2016 ◽  
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.

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

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.

Advances in the study of the mechanochemical coupling of kinesin

2018 ◽  
Vol 32 (18) ◽  
pp. 1840001 ◽  
Author(s):  
Ming Li ◽  
Zhong-Can Ou-Yang ◽  
Yao-Gen Shu
Keyword(s):  
Molecular Dynamics ◽  
Single Molecule ◽  
Intracellular Transport ◽  
Coordination Mechanism ◽  
Personal Perspective ◽  
Long Distance ◽  
Future Studies ◽  
Mechanochemical Coupling ◽  
Dynamics Simulations ◽  
Made In

Kinesin is a two-headed linear motor for intracellular transport. It can walk a long distance in a hand-over-hand manner along the track before detaching (i.e., high processivity), and it consumes one ATP molecule for each step (i.e., tight mechanochemical coupling). The mechanisms of the coordination of its two heads and the mechanochemical coupling are the central issues of numerous researches. A few advances have been made in recent decades, thanks to the development of single-molecule technologies and molecular dynamics simulations. In this paper, we review some progress of the studies on the kinematics, energetics, coordination mechanism, mechanochemical mechanism of kinesin. We also present a personal perspective on the future studies of kinesin.

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

2020 ◽  
Author(s):  
Francesca Ferrari ◽  
Maicol Bissaro ◽  
Simone Fabbian ◽  
Jessica de Almeida Roger ◽  
Stefano Mammi ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Solution Nmr ◽  
Protein Recognition ◽  
Fragment Screening ◽  
Fragment Library ◽  
Dynamics Simulations ◽  
A Prospective Study ◽  
First Time ◽  
Established Technique ◽  
State Of Art

<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>

Absorption of Mechanical Energy via Formation of Ice Nanotubes in Zeolite

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...

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

2017 ◽  
Vol 19 (29) ◽  
pp. 19468-19477 ◽  
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.

scholarly journals The Lazy Life of Lipid-Linked Oligosaccharides in All Life Domains

2019 ◽  
Author(s):  
Pablo Ricardo Arantes ◽  
Conrado Pedebos ◽  
Marcelo D. Poleto ◽  
Laércio Pol-Fachin ◽  
Hugo Verli
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Membrane Lipid ◽  
Membrane Dynamics ◽  
En Bloc ◽  
Future Studies ◽  
Head Groups ◽  
Domains Of Life ◽  
Glycosylation Pathway ◽  
Dynamics Simulations

<div> <div> <div> <p>Lipid-linked oligosaccharides (LLOs) plays an important role in the N-glycosylation pathway as the donor substrate of oligosaccharyltransferases (OSTs), which are respon- sible for the en bloc transfer of glycan chains onto a nascent polypeptide. The lipid component of LLO in both eukarya and archaea consists of a dolichol, and an unde- caprenol in prokarya, whereas the number of isoprene units may change between species. Given the potential relevance of LLOs and their related enzymes to diverse biotechno- logical applications, obtaining reliable LLO models from distinct domains of life could support further studies on complex formation and their processing by OSTs, as well as protein engineering on such systems. In this work, molecular modeling, such as quantum mechanics calculations, molecular dynamics simulations, and metadynamics were employed to study eukaryotic (Glc3-Man9-GlcNAc2-PP-Dolichol), bacterial (Glc1- GalNAc5-Bac1-PP-Undecaprenol) and archaeal (Glc1-Man1-Gal1-Man1-Glc1-Gal1-Glc1- P-Dolichol) LLO in membrane bilayers. Microsecond molecular dynamics simulations and metadynamics calculations of LLOs revealed that glycan chains are more prone to interact with the membrane lipid head groups, while the PP linkages are positioned at the lipid phosphate head groups level. Dynamics of isoprenoid chains embedded within the bilayer are described and membrane dynamics and its related properties are also investigated. Overall, there are similarities regarding the structural and dynamics of the eukaryotic, the bacterial and the archaeal LLOs in bilayers, which can support the comprehension of their association with OSTs. This data may support future studies on the transferring mechanism of the oligosaccharide chain to an acceptor protein. </p> </div> </div> </div>

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

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.

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

CrystEngComm ◽  
2019 ◽  
Vol 21 (42) ◽  
pp. 6354-6364 ◽  
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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