Maximum Bond Length Research Articles

Exploring the structural and molecular interaction landscape of nirmatrelvir and Mpro complex: The study might assist in designing more potent antivirals targeting SARS-CoV-2 and other viruses

BackgroundSeveral therapeutics have been developed and approved against SARS-CoV-2 occasionally; nirmatrelvir is one of them. The drug target of nirmatrelvir is Mpro, and therefore, it is necessary to comprehend the structural and molecular interaction of the Mpro-nirmatrelvir complex. MethodsIntegrative bioinformatics, system biology, and statistical models were used to analyze the macromolecular complex. ResultsUsing two macromolecular complexes, the study illustrated the interactive residues, H-bonds, and interactive interfaces. It informed of six and nine H-bond formations for the first and second complex, respectively.The maximum bond length was observed as 3.33 Å. The ligand binding pocket's surface area and volume were noted as 303.485 Å2 and 295.456 Å3 for the first complex and 308.397 Å2 and 304.865 Å3 for the second complex. The structural proteome dynamics were evaluated by analyzing the complex's NMA mobility, eigenvalues, deformability, and B-factor. Conversely, a model was created to assess the therapeutic status of nirmatrelvir. ConclusionsOur study reveals the structural and molecular interaction landscape of Mpro-nirmatrelvir complex. The study will guide researchers in designing more broad-spectrum antiviral molecules mimicking nirmatrelvir, which assist in fighting against SARS-CoV-2 and other infectious viruses. It will also help to prepare for future epidemics or pandemics.

Revealing the structural and molecular interaction landscape of the favipiravir-RTP and SARS-CoV-2 RdRp complex through integrative bioinformatics: Insights for developing potent drugs targeting SARS-CoV-2 and other viruses

BackgroundThe global research community has made considerable progress in therapeutic and vaccine research during the COVID-19 pandemic. Several therapeutics have been repurposed for the treatment of COVID-19. One such compound is, favipiravir, which was approved for the treatment of influenza viruses, including drug-resistant influenza. Despite the limited information on its molecular activity, clinical trials have attempted to determine the effectiveness of favipiravir in patients with mild to moderate COVID-19. Here, we report the structural and molecular interaction landscape of the macromolecular complex of favipiravir-RTP and SARS-CoV-2 RdRp with the RNA chain. MethodsIntegrative bioinformatics was used to reveal the structural and molecular interaction landscapes of two macromolecular complexes retrieved from RCSB PDB. ResultsWe analyzed the interactive residues, H-bonds, and interaction interfaces to evaluate the structural and molecular interaction landscapes of the two macromolecular complexes. We found seven and six H-bonds in the first and second interaction landscapes, respectively. The maximum bond length is 3.79 Å. In the hydrophobic interactions, five residues (Asp618, Asp760, Thr687, Asp623, and Val557) were associated with the first complex and two residues (Lys73 and Tyr217) were associated with the second complex. The mobilities, collective motion, and B-factor of the two macromolecular complexes were analyzed. Finally, we developed different models, including trees, clusters, and heat maps of antiviral molecules, to evaluate the therapeutic status of favipiravir as an antiviral drug. ConclusionsThe results revealed the structural and molecular interaction landscape of the binding mode of favipiravir with the nsp7–nsp8–nsp12-RNA SARS-CoV-2 RdRp complex. Our findings can help future researchers in understanding the mechanism underlying viral action and guide the design of nucleotide analogs that mimic favipiravir and exhibit greater potency as antiviral drugs against SARS-CoV-2 and other infectious viruses. Thus, our work can help in preparing for future epidemics and pandemics.

The Full Model of Micropipette Aspiration of Cells: A Mesoscopic Simulation.

Studies on the interaction between cells and micromanipulation tools are necessary to optimize the procedures and improve the developmental potential of cells. The molecular dynamics simulation is not possible for such a large-scale simulation, and the spring-damped viscoelastic models and the constitutive equationsof the continuum are usually adopted to model the cells as a whole without consideration of the different properties presented by the heterogeneous subcellular components. In this study, we utilized coarse-grained modeling to develop a subcellular model of suspension cell dynamics and a model of a holding micropipette for the fixation of a suspension cell, and designed a large-scale, accurate mesoscopic simulation environment for specific cell micromanipulation. We established a triangular mesh cell membrane and a uniformly distributed, non-intersecting cytoskeleton network and added polymerization/depolymerization processes to connect the cytoskeleton chains with the membrane and cross-linking proteins. In the cell aspiration model, we adopted the profile of the reversed Poiseuille flow to calibrate the viscosity of the fluid and set the bounce-back condition and the appropriate solid-fluid force coefficient to realize non-slip flow at the boundary. The rheological properties of the cells during micropipette aspiration were further analyzed in the simulation by varying parameters such as the inner diameter of the micropipette, negative pressure, and maximum bond length. The model well reproduced the experimentally observed cell deformation phenomenon at low and high pressures. The dynamic response of the cell elongation observed from the simulation was consistent with that obtained from the analysis of the experimental data collected from a custom-designed micromanipulation system. STATEMENT OF SIGNIFICANCE: In this study, we extended the coarse-grained modeling of cells by developing a relatively large-scale micromanipulation environment consisting of a subcellular cell dynamics model and a fluid flow model for cell aspiration. We simulated cytoskeleton filaments that were uniformly distributed in space via applying Harmonic energy to model cytoskeleton with a high level of fidelity. The shortcoming of the soft repulsion in the solid-fluid interaction in the current simulation technique was solved by implementing the bounce-back boundary and the condition that the total force imposed by the wall particles on the fluid particles was equal to the pressure of the fluid. This work paved the way for understanding the mechanical properties of cells and improving the biological efficacy of micromanipulation.

Molecular dynamics simulation on ε-CL-20 based PBXs with chain-extended poly(3,3-bis(azidomethyl)oxetane)

Molecular dynamics (MD) method was performed on ε-CL-20 based PBXs, which were constructed by embedding different chain-extended poly(3,3-bis(azidomethyl)oxetane)(CE-PBAMO) with ε-CL-20(001) crystalline surface. The binding energy(Ebinding), maximum bond length (Lmax) of the N-NO2 trigger bond, cohesive energy density (CED) and mechanical properties of ε-CL-20 (P0) and PBX systems(P1, P2, P3) were calculated. The order of Ebinding is P3 > P1 > P2, implying that CE-PBAMO with isophorone diisocyanate (IPDI-CE) and ε-CL-20 have better compatibility. Lmax is found to be in the order of P0 > P2 > P1 > P3, which indicates that the addition of polymer binders lowers the sensitivity of the base explosive, and IPDI-CE minimized sensitivity of the base explosive. The order of CED is P0 > P3 > P1 > P2, demonstrating that polymer binders show same tendency in reducing the sensitivity of the base explosive with Lmax calculation. Moreover, mechanical property calculation results reveal that the tensile modulus (E), bulk modulus (K) and shear modulus (G) of pure ε-CL-20 are larger than ε-CL-20 based PBXs, while the values of Cauchy pressure (C12-C44) change a little and increase for ε-CL-20 based PBXs. The calculation of detonation performance shows that ε-CL-20 based PBXs with 5% IPDI-CE possess high power and lower sensitivity.

Molecular Dynamics Simulations for Effects of Fluoropolymer Binder Content in CL-20/TNT Based Polymer-Bonded Explosives.

In order to better understand the role of binder content, molecular dynamics (MD) simulations were performed to study the interfacial interactions, sensitivity and mechanical properties of 2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane/2,4,6-trinitrotoluene (CL-20/TNT) based polymer-bonded explosives (PBXs) with fluorine rubber F2311. The binding energy between CL-20/TNT co-crystal (1 0 0) surface and F2311, pair correlation function, the maximum bond length of the N–NO2 trigger bond, and the mechanical properties of the PBXs were reported. From the calculated binding energy, it was found that binding energy increases with increasing F2311 content. Additionally, according to the results of pair correlation function, it turns out that H–O hydrogen bonds and H–F hydrogen bonds exist between F2311 molecules and the molecules in CL-20/TNT. The length of trigger bond in CL-20/TNT were adopted as theoretical criterion of sensitivity. The maximum bond length of the N–NO2 trigger bond decreased very significantly when the F2311 content increased from 0 to 9.2%. This indicated increasing F2311 content can reduce sensitivity and improve thermal stability. However, the maximum bond length of the N–NO2 trigger bond remained essentially unchanged when the F2311 content was further increased. Additionally, the calculated mechanical data indicated that with the increase in F2311 content, the rigidity of CL-20/TNT based PBXs was decrease, the toughness was improved.

Theoretical studies on CL-20/HMX based energetic composites under external electric field

The response of various CL-20 and HMX based energetic composites to external electric field was studied by molecular dynamics simulations. The results indicate that structural features, energetic properties and mechanical properties of all energetic systems show great dependence on the additives, ratio of CL-20 to HMX and external electric field. The comprehensive analysis about structural features based on trigger bond length distribution, the maximum bond length of trigger bond and radial distribution functions between O and H atoms suggest that additives, ratio of CL-20 to HMX, and external electric field can effectively adjust and improve the stability for the energetic systems. The discussions about energetic properties based on potential energies, cohesive energy density and interaction energy between two N atoms of N-N trigger bond reveal that stability of the energetic systems can be adjusted by adding additives and changing ratio of CL-20 to HMX, and can be enhanced by the introduction of external electric field. Besides, the studies show that mechanical properties can be significantly adjusted and improved by the proportion of main explosives, additives and an external electric field. Our studies may provide an avenue to adjust and improve the performances of energetic materials.

Molecular Dynamics Simulation of the Influence of RDX Internal Defects on Sensitivity

The internal defect is an important factor that could influence the energy and safety properties of energetic materials. RDX samples of two qualities were characterized and simulated to reveal the influence of different defects on sensitivity. The internal defects were characterized with optical microscopy, Raman spectroscopy and microfocus X-ray computed tomography technology. The results show that high-density RDX has fewer defects and a more uniform distribution. Based on the characterization results, defect models with different defect rates and distribution were established. The simulation results show that the models with fewer internal defects lead to shorter N-NO2 maximum bond lengths and greater cohesive energy density (CED). The maximum bond length and CED can be used as the criterion for the relative sensitivity of RDX, and therefore defect models doped with different solvents are established. The results show that the models doped with propylene carbonate and acetone lead to higher sensitivity. This may help to select the solvent to prepare low-sensitivity RDX. The results reported in this paper are aiming at the development of a more convenient and low-cost method for studying the influence of internal defects on the sensitivity of energetic materials.

Computational analysis the relationships of energy and mechanical properties with sensitivity for FOX-7 based PBXs via MD simulation.

Molecular dynamics (MD) simulations have been applied to investigate 1, 1-diamino-2, 2-dinitroethene (FOX-7) crystal and FOX-7 (011)-based polymer-bonded explosives (PBXs) with four typical polymers, polyethylene glycol (PEG), fluorine-polymer (F2603), ethylene-vinyl acetate copolymer (EVA) and ester urethane (ESTANE5703) under COMPASS force field. Binding energy (Ebind), cohesive energy density (CED), initiation bond length distribution, RDG analysis and isotropic mechanical properties of FOX-7 and its PBXs at different temperatures were reported for the first time, and the relationship between them and sensitivity. Using quantum chemistry, FOX-7 was optimized with the four polymers at the B3LYP/6-311++G(d,p) level, and the structure and RDG of the optimized composite system were analysed. The results indicated that the binding energy presented irregular changes with the increase in temperature. The order of binding ability of different binders to the FOX-7 (011) crystal surface is PEG > ESTANE5703 > EVA > F2603. When the temperature increases, the maximum bond length (Lmax) of the induced bond increases and the CED decreases. This result is achieved in agreement with the known experimental fact that the sensitivity of explosives increases with temperature, and they can be used as the criterion to predict the sensitivity of explosives. The descending order of Lmax is FOX-7 > F2603 > ESTANE5703≈EVA > PEG. The intermolecular interactions between FOX-7 and the four polymers were mainly weak hydrogen bonding and van der Waals interactions, and these interactions helped to reduce the bond length of C-NO2, leading to a decrease in the sensitivity of FOX-7. The addition of polymers can effectively improve the mechanical properties of explosives. Among the four polymers, EVA has the best effect on improving the mechanical properties of FOX-7 (011). At the same temperature, the modulus can be used to predict the sensitivity of high-energy materials. Cauchy pressure can predict the sensitivity of non-brittle energetic materials. The nature of the interaction between FOX-7 and the four polymers is hydrogen bonding and van der Waals force, of which hydrogen bonding is the main one. These studies are meaningful for the formulation design and sensitivity prediction of FOX-7 and its PBXs.

External electric field induced conformational changes as a buffer to increase the stability of CL-20/HMX cocrystal and its pure components

As a significant stimulus, the external electric field (EEF) plays a vital role in affecting the behaviors of energetic materials (EMs). We investigated the effects of the EEF on CL-20/HMX cocrystal and its pure components by molecular dynamics simulations. The COMPASS force field, atom-based summation method for van der Waals interactions, and Ewald summation method for electrostatic forces were applied. The results show that there exists sudden conformational changes at the EEF intensity of 0.3 and 0.9 V/Å for β-HMX and ε-CL-20, respectively, while the EEF-induced conformational change in CL-20/HMX is a gradual process. The analysis of the N-NO2 bond length distributions, radial distribution functions (RDFs) of the intermolecular O⋯H atom pair, and cohesive energy density (CED) reveals that the EEF can remarkably decrease the N-NO2 bond length and enhance hydrogen bonding interactions in the systems. A comprehensive analysis of the structural stability based on the maximum bond length of the trigger bond (Lmax), the interaction energy between two N atoms of the NN trigger bond (EN-N), and mechanical properties indicates that EEF can effectively improve the stability of the systems. These findings provide basic insights into the comprehensive understanding of the effects of the EEF on the EMs.

Capacidad de anclaje de los split sets en función de su longitud efectiva de anclaje

The support in underground excavations is essential to preserve the life and health of the workers, damage to the equipment and to have proper progress of the excavation. The most common Rock support sets are the rock bolts, temporary or definitive. Among temporary rock bolts, there are the Split sets, widespread around the world due to their ease of installation and cheaper. Split Sets, have the appearance of a tube with a 15 mm slot in its entire length, manufacturers and suppliers recommended 38 mm diameter of drill holes and depths according to their length. In this research, the ground and holes were simulated with a special table and steel tubes. Split Sets, were conditioned to make anchors of 1, 2, 3, and 4 feet of bond length. Prepared the simulator tubes and Split Sets were installed, after which, were performed the pull test of the 3 samples for each bond length to determine their anchor capacity. Peak loads for each length researched were recorded in formats designed for this purpose. Compiling the recorded values and adjusting them according to certification of pressure gauge calibration carried out in UNI, obtained the anchor capacity for each of length tested. Results that have been captured in a table and graph, where is inferred that the anchor capacity of the Split Sets is affected by its bond length, and that do not have a relationship. Maximum bond length of anchorage tends to 4 feet, i.e., it is unnecessary to use greater lengths.

Molecular Dynamics Simulation Studies of the CL-20/DNB Co-crystal

Molecular dynamics (MD) simulation was conducted for a DNB (1,3-dinitrobenzene) crystal, a e-CL-20 (2,4,6,8,10,12-hexanitro-2,4,6,8,10,12- hexaazaisowurtzitane) crystal, a CL-20/DNB co-crystal and a CL-20/DNB composite. From the calculated maximum bond length (Lmax) of the N−NO2 trigger bond, the cohesive energy density (CED) and the binding energy (Ebind), it was found that the CL-20/DNB co-crystal is more insensitive than its composite. Its thermal stability is also better than that of its composite. The pair correlation function (PCF) analysis method was applied to investigate the interfaces between different molecular layers in the CL-20/DNB co-crystal, and in the composite. Additionally, the calculated mechanical data showed that the moduli of the CL-20/DNB co-crystal and its composite are smaller and their elastic elongation and ductility are better than those of the e-CL-20 and DNB crystals.

Torsional behavior of single-walled carbon nanotubes

Atomistic simulations were performed to investigate the deformation behavior of single-walled carbon nano-tubes (SWCNTs) under torsional loading. The evolutions of the potential energy and stresses were presented. Radial distribution functions (RDFs) were calculated to analyze structural evolution during torsional deformation. The results show that during torsion, the tensile stress component along the tube axis is most significant and other stress components are almost negligible. The tensile stress stretched the C–C bonds until they reached the bond length of 0.18nm. The torsional strength of the SWCNTs is about 30% of the tensile strength. Buckling took place at a few degrees of torsional angle and propagated along the tube as the torsional angle increased, and collapse of the tube wall followed buckling. These structural evolutions can be well described with the RDFs. Two new peaks appeared at 0.21nm and 0.18nm in the RDFs, corresponding to the minimum spacing between the atoms in the collapsed layers, and the maximum bond length that can be reached in stretching before rupture.

Comparative study on structure, energetic and mechanical properties of a ε-CL-20/HMX cocrystal and its composite with molecular dynamics simulation

Molecular dynamics (MD) simulation was conducted for a ε-CL-20 (2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexazisowurtzitane) crystal, a β-HMX (1,3,5,7-tetranitro-1,3,5,7-tetrazocane) crystal, a ε-CL-20/HMX cocrystal and its composite with the same molar ratio as in the cocrystal using a COMPASS force field with NPT ensemble at different temperatures. The maximum bond length (Lmax) of the N–NO2 trigger bond, cohesive energy density (CED) and binding energy (Ebind) between HMX and CL-20 molecules as well as elastic properties were calculated. Lmax increases with rising temperature and is found to be in the order of ε-CL-20/HMX cocrystal < CL-20/HMX composite < ε-CL-20 crystal at the same temperature. CED and Ebind of the cocrystal decrease with increasing temperature and are all greater than those of the composite at the same temperature. These indicate that the cocrystal is the most insensitive and its thermal stability is better than that of the composite. Furthermore, the pair correlation function g(r) analysis reveals that hydrogen bonds exist. The tensile modulus (E), bulk modulus (K) and shear modulus (G) of the ε-CL-20/HMX cocrystal and the composite are smaller than those of ε-CL-20 and β-HMX crystals and decrease with increasing temperature. However, the K/G values of the cocrystal and the composite are larger than those of the other two crystals, implying that they have better ductility.

Molecular dynamics study on the relationships of modeling, structural and energy properties with sensitivity for RDX-based PBXs

In this paper, a primary model is established for MD (molecular dynamics) simulation for the PBXs (polymer-bonded explosives) with RDX (cyclotrimethylene trinitramine) as base explosive and PS as polymer binder. A series of results from the MD simulation are compared between two PBX models, which are represented by PBX1 and PBX2, respectively, including one PS molecular chain having 46 repeating units and two PS molecular chains with each having 23 repeating units. It has been found that their structural, interaction energy and mechanical properties are basically consistent between the two models. A systematic MD study for the PBX2 is performed under NPT conditions at five different temperatures, i.e., 195 K, 245 K, 295 K, 345 K, and 395 K. We have found that with the temperature increase, the maximum bond length (Lmax) of RDX N−N trigger bond increases, and the interaction energy (EN-N) between two N atoms of the N−N trigger bond and the cohesive energy density (CED) decrease. These phenomena agree with the experimental fact that the PBX becomes more sensitive as the temperature increases. Therefore, we propose to use the maximum bond length Lmax of the trigger bond of the easily decomposed and exploded component and the interaction energy EN-N of the two relevant atoms as theoretical criteria to judge or predict the relative degree of heat and impact sensitivity for the energetic composites such as PBXs and solid propellants.

Study on structure, sensitivity and mechanical properties of HMX and HMX-based PBXs with molecular dynamics simulation

Molecular dynamics simulation was applied to investigate structures, sensitivity and mechanical properties of β-HMX (β-cyclotetramethylene tetranitramine) crystal and β-HMX based PBXs (polymer-bonded explosives) with F2311 polymer binder. The NNO2 trigger bond lengths of the HMX and its PBXs were obtained under different temperatures, and discussed in terms of their relations with sensitivity. Mechanical properties were also calculated at different temperatures, based on which, their relations with the sensitivity were discussed. It finds that the maximum bond length Lmax of NNO2 trigger bond is an important structural parameter to effectively judge the sensitivity, the mechanical properties correlate well with the sensitivity, and especially, Cauchy pressure is an important mechanical parameter that can be used to effectively evaluate the sensitivity.

The Relation between Bond Lengths and Dissociation Energies of Carbon−Carbon Bonds

Bond lengths (r, A) of typical carbon−carbon bonds correlate linearly with bond dissociation energies (BDEs) in the full range of single, double, triple, and highly strained bonds, with BDEs ranging from 16 to 230 kcal mol-1. The equation is r = 1.748−0.002371(BDE), tested with 41 typical carbon−carbon bonds, ranging in length from 1.20 to 1.71 A. This sets a maximum bond length limit of 1.75 A for carbon−carbon bonds.

C 22H 46: The smallest open 3 1-knotted alkane by computer-aided design

The program MolKnot [Chem. Phys. Lett. 433 (2007) 422–426] has been used in order to detect the smallest ever-reported alkane configured to an open-knotted shape with three crossings (3 1). High level ab initio calculations support our findings that 22 carbon atoms are enough to create a knotted polyethylene strand with open ends. These tight open molecular knots exhibit unusually distorted geometric characteristics as multiple extended CC bonds (maximum bond length ∼1.70 Å) and several large C C ˆ C bond angles (maximum bond angle ∼145°). The energy decomposition shows that the strain mainly affects the valence angles of the entangled structure. We observed that this 22-knotted carbon atoms’ region remained almost intact as a part of alkanes with longer chain lengths.

Effect of impurities on the breaking of Au nanowires

Using ab initio density functional theory total energy calculations, we study the influence of H, B, C, N, O, and S in the rupture of a gold nanowire. In particular, using an as realistic as possible model for a suspended gold nanowire under stress, we observe that the Au wire always breaks at an Au–Au bond, with a maximum bond length between 3.0 and 3.1 Å. Therefore, the experimentally observed large Au–Au bonds before the rupture of the nanowire (≈3.6 Å) are probably due to the presence of light impurities (X) forming Au–X–Au bonds. We obtain that the maximum Au–Au distance, for X equals C or N, is of the order of 3.9 Å, whereas for B and O it is of the order of 4.1 Å. On the other hand, for H this maximum distance before the rupture of the wire is approximately 3.6 Å, being the best candidate to explain the experimental results. For both C and H impurities, we present a detailed analysis of the neck atoms electronic structures, and compare them with similar results for the pure nanowire.

Exact solution for a chainlike cluster growth model.

We present an exact solution for a cluster growth model, describing chainlike histories with ordered bond measure and external constraint connected to maximum bond length. We analyze in detail the physical applications that are connected to the parameter regions, where the dominant interparticle interactions are of short-range type.