Structural Properties of G,T-Parallel Duplexes

The structure of G,T-parallel-stranded duplexes of DNA carrying similar amounts of adenine and guanine residues is studied by means of molecular dynamics (MD) simulations and UV- and CD spectroscopies. In addition the impact of the substitution of adenine by 8-aminoadenine and guanine by 8-aminoguanine is analyzed. The presence of 8-aminoadenine and 8-aminoguanine stabilizes the parallel duplex structure. Binding of these oligonucleotides to their target polypyrimidine sequences to form the corresponding G,T-parallel triplex was not observed. Instead, when unmodified parallel-stranded duplexes were mixed with their polypyrimidine target, an interstrand Watson-Crick duplex was formed. As predicted by theoretical calculations parallel-stranded duplexes carrying 8-aminopurines did not bind to their target. The preference for the parallel-duplex over the Watson-Crick antiparallel duplex is attributed to the strong stabilization of the parallel duplex produced by the 8-aminopurines. Theoretical studies show that the isomorphism of the triads is crucial for the stability of the parallel triplex.

Download Full-text

Structural genomics approach to investigate deleterious impact of nsSNPs in conserved telomere maintenance component 1

Scientific Reports ◽

10.1038/s41598-021-89450-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Arunabh Choudhury ◽

Taj Mohammad ◽

Nikhil Samarth ◽

Afzal Hussain ◽

Md. Tabish Rehman ◽

...

Keyword(s):

Noncovalent Interactions ◽

Md Simulations ◽

Telomere Maintenance ◽

Nucleotide Polymorphisms ◽

Telomeric Dna ◽

Congenital Diseases ◽

Ob Fold ◽

Significant Conformational Change ◽

The Stability ◽

The Impact

AbstractConserved telomere maintenance component 1 (CTC1) is an important component of the CST (CTC1-STN1-TEN1) complex, involved in maintaining the stability of telomeric DNA. Several non-synonymous single-nucleotide polymorphisms (nsSNPs) in CTC1 have been reported to cause Coats plus syndrome and Dyskeratosis congenital diseases. Here, we have performed sequence and structure analyses of nsSNPs of CTC1 using state-of-the-art computational methods. The structure-based study focuses on the C-terminal OB-fold region of CTC1. There are 11 pathogenic mutations identified, and detailed structural analyses were performed. These mutations cause a significant disruption of noncovalent interactions, which may be a possible reason for CTC1 instability and consequent diseases. To see the impact of such mutations on the protein conformation, all-atom molecular dynamics (MD) simulations of CTC1-wild-type (WT) and two of the selected mutations, R806C and R806L for 200 ns, were carried out. A significant conformational change in the structure of the R806C mutant was observed. This study provides a valuable direction to understand the molecular basis of CTC1 dysfunction in disease progression, including Coats plus syndrome.

Download Full-text

Molecular Dynamics Studies on the Growth and Structural Properties of Hydrogenated DLC Films

Key Engineering Materials ◽

10.4028/www.scientific.net/kem.373-374.108 ◽

2008 ◽

Vol 373-374 ◽

pp. 108-112

Author(s):

Yu Jun Zhang ◽

Guang Neng Dong ◽

Jun Hong Mao ◽

You Bai Xie

Keyword(s):

Molecular Dynamics ◽

Structural Properties ◽

Impact Energy ◽

Frictional Coefficient ◽

Carbon Films ◽

Dynamics Simulation ◽

Diamond Surface ◽

Hydrogen Atoms ◽

Molecular Configuration ◽

The Impact

The novel frictional properties of hydrogenated DLC (Diamond-like Carbon) films have been reported for nearly ten years. But up to now, researchers still haven’t known the exact mechanism resulting in the super-low frictional performance of hydrogenated DLC films. Especially they have little knowledge on the molecular configuration and structural properties of these kinds of films. In this paper, CH3 radicals with different impact energies are selected as source species to deposit DLC films on diamond (100) by molecular dynamics simulation. Results show hydrogenated DLC films can be successfully obtained when impact energy is in an appropriate scope that is no less than 20eV. The depositing processes involve impinging diamond surface and bonding procedure. Some atoms, instead of bonding with substrate atoms, fly away from the diamond surface. Only suitable impact energy can improve the growth of the film. Within 30eV to 60eV, the maximum deposition ratio is attained. In addition, when carbon atoms act as the deposition sources, the deposition ratio is relatively higher. Furthermore, the authors find that species with higher concentration of carbon atoms in deposition sources lead to a better deposition rate. Carbon atoms are more reactive than hydrogen atoms. Then the relative densities of DLC films are calculated. The density curves indicate that the structures of the films vary obviously as the impact energy augments. The average relative density is generally monotone increase with the increment of impact energy. The hybridization of carbon atoms greatly affects the properties of hydrogenated DLC films. The transition between sp2 and sp3 will result in the graphitization and reduce the frictional coefficient when DLC films are used as tribo-pair in friction.

Download Full-text

Atomistic Analysis of ToxN and ToxI Complex Unbinding Mechanism

International Journal of Molecular Sciences ◽

10.3390/ijms19113524 ◽

2018 ◽

Vol 19 (11) ◽

pp. 3524 ◽

Cited By ~ 6

Author(s):

Guodong Hu ◽

Xiu Yu ◽

Yunqiang Bian ◽

Zanxia Cao ◽

Shicai Xu ◽

...

Keyword(s):

Molecular Dynamics ◽

Noncoding Rna ◽

Md Simulations ◽

Normal Function ◽

Toxin Complex ◽

Potentials Of Mean Force ◽

Protein Toxins ◽

Function Relationship ◽

The Stability ◽

Smd Simulations

ToxIN is a triangular structure formed by three protein toxins (ToxNs) and three specific noncoding RNA antitoxins (ToxIs). To respond to stimuli, ToxI is preferentially degraded, releasing the ToxN. Thus, the dynamic character is essential in the normal function interactions between ToxN and ToxI. Here, equilibrated molecular dynamics (MD) simulations were performed to study the stability of ToxN and ToxI. The results indicate that ToxI adjusts the conformation of 3′ and 5′ termini to bind to ToxN. Steered molecular dynamics (SMD) simulations combined with the recently developed thermodynamic integration in 3nD (TI3nD) method were carried out to investigate ToxN unbinding from the ToxIN complex. The potentials of mean force (PMFs) and atomistic pictures suggest the unbinding mechanism as follows: (1) dissociation of the 5′ terminus from ToxN, (2) missing the interactions involved in the 3′ terminus of ToxI without three nucleotides (G31, A32, and A33), (3) starting to unfold for ToxI, (4) leaving the binding package of ToxN for three nucleotides of ToxI, (5) unfolding of ToxI. This work provides information on the structure-function relationship at the atomistic level, which is helpful for designing new potent antibacterial drugs in the future.

Download Full-text

Understanding the Pyrimethamine Drug Resistance Mechanism via Combined Molecular Dynamics and Dynamic Residue Network Analysis

Molecules ◽

10.3390/molecules25040904 ◽

2020 ◽

Vol 25 (4) ◽

pp. 904 ◽

Cited By ~ 1

Author(s):

Arnold Amusengeri ◽

Rolland Bantar Tata ◽

Özlem Tastan Bishop

Keyword(s):

Molecular Dynamics ◽

Drug Resistance ◽

Network Analysis ◽

Binding Free Energy ◽

Resistance Mechanism ◽

Point Mutations ◽

Md Simulations ◽

Conformational Plasticity ◽

New Perspective ◽

The Impact

In this era of precision medicine, insights into the resistance mechanism of drugs are integral for the development of potent therapeutics. Here, we sought to understand the contribution of four point mutations (N51I, C59R, S108N, and I164L) within the active site of the malaria parasite enzyme dihydrofolate reductase (DHFR) towards the resistance of the antimalarial drug pyrimethamine. Homology modeling was used to obtain full-length models of wild type (WT) and mutant DHFR. Molecular docking was employed to dock pyrimethamine onto the generated structures. Subsequent all-atom molecular dynamics (MD) simulations and binding free-energy computations highlighted that pyrimethamine’s stability and affinity inversely relates to the number of mutations within its binding site and, hence, resistance severity. Generally, mutations led to reduced binding affinity to pyrimethamine and increased conformational plasticity of DHFR. Next, dynamic residue network analysis (DRN) was applied to determine the impact of mutations and pyrimethamine binding on communication dispositions of DHFR residues. DRN revealed residues with distinctive communication profiles, distinguishing WT from drug-resistant mutants as well as pyrimethamine-bound from pyrimethamine-free models. Our results provide a new perspective on the understanding of mutation-induced drug resistance.

Download Full-text

Comparison of the effect of poly(N-vinyl caprolactam) and poly(N-isopropyl acrylamide) trimers on the stability of hydrated Na-montmorillonite: A molecular dynamics study

Polymers and Polymer Composites ◽

10.1177/0967391120935249 ◽

2020 ◽

pp. 096739112093524

Author(s):

Jiafang Xu ◽

Moussa Camara ◽

Hualin Liao ◽

Hong Guo ◽

Kouassi Louis Kra ◽

...

Keyword(s):

Molecular Dynamics ◽

Conformational Changes ◽

Stable State ◽

Dynamics Simulation ◽

Effect Of Temperature ◽

Radius Of Gyration ◽

Molecular Arrangement ◽

Isopropyl Acrylamide ◽

The Stability ◽

The Impact

In the present study, we performed a molecular dynamics simulation of the intercalation of poly( N-isopropyl acrylamide) (NIPAM)3 and poly( N-vinyl caprolactam) (NVCL)3 trimers into Na-montmorillonite (Na-Mt) to evaluate their effects on the interlayer structure and the stability of hydrated Na-Mt. The impact of both trimers on the interlayer species and their dynamics properties at different temperatures in a canonical ensemble (NVT) were investigated. The results showed that the electrostatic forces exerted by Na cations on H2O molecules and the interlayer H2O molecular arrangement are not affected by the rise in temperature after adding both trimers. Trimer addition reinforced the structure of interlayer H2O molecules so that the effect of temperature increase on them became negligible. The structural dynamics evolution of the radius of gyration of both trimers showed the existence of conformation changes when temperature increased. These conformational changes are more complex in the case of (NVCL)3 than (NIPAM)3 due to its large monomers. Both trimers reduced the mobility of interlayer particles with a better inhibition effect obtained for (NVCL)3 compared to (NIPAM)3. The concentration profile of interlayers’ species showed the affinity of Na cations for clay mineral surfaces while H2O molecules moved away. Compared these two trimers, the most stable state of Na-Mt is achieved with (NVCL)3. These results could help highlight the inhibition properties of (NIPAM)3 and (NVCL)3 on hydrated Na-Mt and to predict its stability against changes in environmental conditions.

Download Full-text

Molecular Dynamics Study Of Surface Morphological Evolution By Cluster Impacts

MRS Proceedings ◽

10.1557/proc-792-r4.7 ◽

2003 ◽

Vol 792 ◽

Author(s):

Takaaki Aoki ◽

Jiro Matsuo ◽

Isao Yamada

Keyword(s):

Molecular Dynamics ◽

Ion Irradiation ◽

Morphological Evolution ◽

Md Simulations ◽

Impact Area ◽

Cluster Ion ◽

Dynamics Simulations ◽

Large Clusters ◽

The Hill ◽

The Impact

ABSTRACTIn order to understand the characteristics of surface modification process with cluster ion irradiation, molecular dynamics simulations of Ar cluster impacting on Si surface with various surface structures were carried out. It was found that the surface morphology is dynamically deformed with only one cluster impact and the impact process of cluster is different depending on the local surface structure. For example, when an Ar2000 cluster accelerated with 20keV impacted on the convex point of the surface, the hill was compressed and the impact area was smoothed. At the impact on a concave point, a deeper crater was formed compared with the impact on a flat surface. On the other hand, the MD simulations of sequential impacts of large clusters were performed. It was found that the small tip structures on the surface could be removed easily with cluster irradiation. It was shown that surface roughness converges to 15∼20Å and this value agrees with the result obtained by single impact of cluster.

Download Full-text

Crystal structures and dynamical properties of dense CO2

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1601254113 ◽

2016 ◽

Vol 113 (40) ◽

pp. 11110-11115 ◽

Cited By ~ 21

Author(s):

Xue Yong ◽

Hanyu Liu ◽

Min Wu ◽

Yansun Yao ◽

John S. Tse ◽

...

Keyword(s):

High Pressure ◽

High Pressures ◽

Theoretical Calculations ◽

Ambient Pressure ◽

Md Simulations ◽

Ab Initio Molecular Dynamics ◽

Structural Polymorphism ◽

Stability Structure ◽

Dynamical Properties ◽

The Stability

Structural polymorphism in dense carbon dioxide (CO2) has attracted significant attention in high-pressure physics and chemistry for the past two decades. Here, we have performed high-pressure experiments and first-principles theoretical calculations to investigate the stability, structure, and dynamical properties of dense CO2. We found evidence that CO2-V with the 4-coordinated extended structure can be quenched to ambient pressure below 200 K—the melting temperature of CO2-I. CO2-V is a fully coordinated structure formed from a molecular solid at high pressure and recovered at ambient pressure. Apart from confirming the metastability of CO2-V (I-42d) at ambient pressure at low temperature, results of ab initio molecular dynamics and metadynamics (MD) simulations provided insights into the transformation processes and structural relationship from the molecular to the extended phases. In addition, the simulation also predicted a phase V′(Pna21) in the stability region of CO2-V with a diffraction pattern similar to that previously assigned to the CO2-V (P212121) structure. Both CO2-V and -V′ are predicted to be recoverable and hard with a Vicker hardness of ∼20 GPa. Significantly, MD simulations found that the CO2 in phase IV exhibits large-amplitude bending motions at finite temperatures and high pressures. This finding helps to explain the discrepancy between earlier predicted static structures and experiments. MD simulations clearly indicate temperature effects are critical to understanding the high-pressure behaviors of dense CO2 structures—highlighting the significance of chemical kinetics associated with the transformations.

Download Full-text

Molecular Dynamics Simulations of Cluster-size Effect on Sputtering Process with Reactive Gas Cluster Ions

MRS Proceedings ◽

10.1557/proc-0908-oo05-07 ◽

2005 ◽

Vol 908 ◽

Author(s):

Takaaki Aoki ◽

Jiro Matsuo

Keyword(s):

Molecular Dynamics ◽

Size Effect ◽

Cluster Size ◽

Incident Energy ◽

Md Simulations ◽

Cluster Ions ◽

Experimental Conditions ◽

Near Surface ◽

The Impact ◽

Reactive Cluster

AbstractTo investigate the size-effect of reactive clusters on sputtering processes, we performed molecular dynamics (MD) simulations of reactive cluster ions with various sizes impacting on solid targets. Various sizes of fluorine clusters, (F2)30, (F2)300 and (F2)3000, were irradiated on a Si(100) target at the same total incident energy of 6 keV. These clusters were irradiated on the same target one after another in order to reproduce real experimental conditions such as the accumulation of fluorine atoms in the target. The MD simulations of sequential cluster impacts enabled to perform various statistical analyses regarding the sputtered particles. The study of cluster size distributions showed that the sputtering process by reactive cluster ion impact has similarity with the emission from quasi-liquid materials excited to hyper-thermal conditions by ion bombardment. However, the major sputtered particles were different with each other; Si for (F2)30 (100 eV/atom), SiF2 for (F2)300 (10 eV/atom), and SiF3 for (F2)3000 (1 eV/atom). At the impact of a large size cluster with low incident energy, a large number of Si-F bondings were generated at the cluster-target interface surface, which enhances formation of volatile SiFx compounds with many fluorine atoms. In contrast, a small cluster with high kinetic energy-per-atom could cause the formation of numerous energetic surface atoms at the near surface region, which could be sputtered without being well fluoridated.

Download Full-text

Stability of Two-quartet G-quadruplexes and Their Dimers in Atomistic Simulations

10.1101/820852 ◽

2019 ◽

Cited By ~ 1

Author(s):

Barira Islam ◽

Petr Stadlbauer ◽

Michaela Vorlíčková ◽

Jean-Louis Mergny ◽

Michal Otyepka ◽

...

Keyword(s):

Molecular Dynamics ◽

Md Simulations ◽

The Other ◽

Atomistic Simulations ◽

Structural Element ◽

Dna And Rna ◽

Open Issue ◽

Water Models ◽

Weakly Stable ◽

The Stability

ABSTRACTG-quadruplexes (GQs) are four-stranded non-canonical DNA and RNA architectures that can be formed by guanine-rich sequences. The stability of GQs increases with the number of G-quartets and three G-quartets generally form stable GQs. However, the stability of two-quartet GQs is an open issue. To understand the intrinsic stability of two-quartet GQ stems, we have carried out a series of unbiased molecular dynamics (MD) simulations (∼505 µs in total) of two- and four-quartet DNA and RNA GQs, with attention paid mainly to parallel-stranded arrangements. We used AMBER DNA parmOL15 and RNA parmOL3 force fields and tested different ion and water models. DNA two-quartet parallel-stranded GQs unfolded in all the simulations while the equivalent RNA GQ was stable in most of the simulations. GQs composed of two stacked units of two-quartet GQs were stable for both DNA and RNA. The simulations suggest that a minimum of three quartets are needed to form an intrinsically stable all-anti parallel-stranded DNA GQ. Parallel two-quartet DNA GQ may exist if substantially stabilized by another molecule or structural element, including multimerisation. On the other hand, we predict that isolated RNA two-quartet parallel GQs may form, albeit being weakly stable. We also show that ionic parameters and water models should be chosen with caution because some parameter combinations can cause spurious instability of GQ stems. Some in-so-far unnoticed limitations of force-field description of multiple ions inside the GQs are discussed, which compromise capability of simulations to fully capture the effect of increase of the number of quartets on the GQ stability.

Download Full-text

Stability of bucket movement and directionof movement of the continuous unit to form the underlying layer of the road

The Russian Automobile and Highway Industry Journal ◽

10.26518/2071-7296-2021-18-4-364-376 ◽

2021 ◽

Vol 18 (4) ◽

pp. 364-376

Author(s):

V. A. Nikolaev

Keyword(s):

Theoretical Studies ◽

Energy Device ◽

Automatic Adjustment ◽

Nominal Pressure ◽

Hydraulic Cylinders ◽

Direction Of Movement ◽

Thrust Vector ◽

The Stability ◽

The Right ◽

The Impact

Introduction. The unit of continuous action for the formation of the underlying layer is designed to increase labor productivity in the construction of roads and other objects, for the construction of which it is necessary to remove the upper layer of soil. The working bodies of the unit are buckets that cut and transport soil. To balance these forces and moments in the transverse-vertical plane, relative to the direction of movement of the buckets, support bars with support hydraulic cylinders are used. To create and regulate the pressure in the support hydraulic cylinders, two hydraulic pneumatic accumulators for controlling the supporting strips are installed on the power device. Part of the forces and moments through the supporting strips, support hydraulic cylinders, the frame of the working part of the unit is transmitted to the energy device that serves to drive the unit. During the operation of the unit, the resistance of the soil to cutting changes continuously. Therefore, the forces and moments transmitted to the energy device change. During operation, the stability of the rectilinear course of the unit is necessary. To ensure the stability of the movement of buckets and the direction of movement of the unit, you should first consider the process of filling the buckets with soil.The method of research. On the basis of the constructive layout, the number of buckets filled with soil was revealed. Suppose the filling of buckets with soil occurs gradually and evenly. Hence, an increase in the load on the right and left support bar was revealed by each subsequent bucket as it is filled. By adding the vertical forces, the value and position of the total load on the supporting bars are determined. The resistance to the movement of the left and right wheels of the working part of the unit, due to the load from the buckets to the supporting strips, the gravity of the raised soil, the gravity of the working part of the unit, is determined. The total horizontal force, the impact of soil on the buckets, directed along the course of the unit, was revealed. The method of calculating the position of the thrust vector of the energy device is given.Results. On the basis of the developed technique, the diameters of the support hydraulic cylinders and the nominal pressure in the hydraulic pneumatic accumulators of the control of the right and left support strips were determined. A constructive layout of the hinged energy device and a system for automatic adjustment of the position of the thrust vector of the energy device depending on the properties of the developed soil is proposed.Conclusion. On the basis of theoretical studies, the diameters of the support hydraulic cylinders and the nominal pressure in the hydraulic pneumatic accumulators of the control of the right and left support strips were calculated. An example of calculating the position of the thrust vector of an energy device is given. The constructive arrangement of the system of automatic adjustment of the position of the thrust vector of the energy device depending on the properties of the developed soil and the general layout of the energy device is proposed. The conducted theoretical studies allow to ensure the stability of the movement of buckets and the direction of movement of the continuous unit for the formation of the underlying layer of roads.

Download Full-text