Normal Mode Analysis Research Articles

Throughflow effect on bi-disperse convection in Rivlin-Ericksen fluid

In this investigation, we delve into the influence of throughflow on the phenomenon of bi-disperse convection within Rivlin-Ericksen fluid. In the context of examining bi-disperse convection within this specific type of fluid, the throughflow effect is considered to have a uniform vertical distribution. The primary focus of this study centers on evaluating the system’s linear stability. To achieve this, we employ normal mode analysis to compute the Darcy-Rayleigh number at the onset of convection. This Darcy-Rayleigh number is computed for both stationary and oscillatory convection modes. Furthermore, we conduct a comprehensive analysis and present the results in graphical form to illustrate the impact of various parameters, including Peclet number and kinematic viscoelastic parameter, on both stationary and oscillatory convection. Our research findings demonstrate that when Peclet number Pr1 < 0, it leads to destabilising effect on both stationary and oscillatory convections. Conversely, when Peclet number Pr1 > 0, it induces stabilising effect on both stationary as well as oscillatory convections.

Repurposing FDA approved drugs against monkeypox virus DNA dependent RNA polymerase: virtual screening, normal mode analysis and molecular dynamics simulation studies.

Zoonotic monkeypox disease, caused by the double-stranded DNA monkeypox virus, has become a global concern. Due to the absence of a specific small molecule drug for the disease, this report aims to identify potential inhibitor drugs for monkeypox. This study explores a drug repurposing strategy using virtual screening to evaluate 1615 FDAapproved drugs against the monkeypox virus DNA dependent RNA polymerase subunit A6R. Normal mode analysis and molecular dynamics simulation assessed the flexibility and stability of the target protein in complex with the top screened drugs. The analysis identified Nilotinib (ZINC000006716957), Conivaptan (ZINC000012503187), and Ponatinib (ZINC000036701290) as the most potential RNA polymerase inhibitors with binding energies of - 7.5kcal/mol. These drugs mainly established hydrogen bonds and hydrophobic interactions with the protein active sites, including LEU95, LEU90, PRO96, MET110, and VAL113, and residues nearby. Normal mode analysis and molecular dynamics simulation confirmed the stability of interactions between the top drugs and the protein. In conclusion, we have discovered promising drugs that can potentially control the monkeypox virus and should be further explored through experimental assays and clinical trials to assess their actual activity against the disease. The findings of this study could lay the foundation for screening repurposed compounds as possible antiviral treatments against various highly pathogenic viruses.

Normal Mode Analysis Elicits Conformational Shifts in Proteins at Both Proximal and Distal Regions to the Phosphosite Stemming from Single-Site Phosphorylation.

Phosphorylation, a fundamental biochemical switch, intricately regulates protein function and signaling pathways. Our study employs extensive computational structural analyses on a curated data set of phosphorylated and unphosphorylated protein pairs to explore the multifaceted impact of phosphorylation on protein conformation. Using normal mode analysis (NMA), we investigated changes in protein flexibility post-phosphorylation, highlighting an enhanced level of structural dynamism. Our findings reveal that phosphorylation induces not only local changes at the phosphorylation site but also extensive alterations in distant regions, showcasing its far-reaching influence on protein structure-dynamics. Through in-depth case studies on polyubiquitin B and glycogen synthase kinase-3 beta, we elucidate how phosphorylation at distinct sites leads to variable structural and dynamic modifications, potentially dictating functional outcomes. While phosphorylation largely preserves the residue motion correlation, it significantly disrupts low-frequency global modes, presenting a dualistic impact on protein dynamics. We also explored alterations in the total accessible surface area (ASA), emphasizing region-specific changes around phosphorylation sites. This study sheds light on phosphorylation-induced conformational changes, dynamic modulation, and surface accessibility alterations, leveraging an integrated computational approach with RMSD, NMA, and ASA, thereby contributing to a comprehensive understanding of cellular regulation and suggesting promising avenues for therapeutic interventions.

Effects of variable gravity on stability in couple-stress fluids across various conducting boundaries

This work aims to inspect the effect of variable gravity field on the convective stability of couple stress fluid for different combinations of bounding surfaces. Both linear and nonlinear analyses are conducted to obtain eigenvalue problems. For this analysis, three different combinations of bounding surfaces have been considered. Normal mode analysis is used for linear analysis, while the energy method is used for nonlinear analysis. The numerical values of critical Rayleigh numbers are calculated using the single-term Galerkin technique. It is found that the Rayleigh numbers for the two analyses coincide, suggesting global stability. It is found that the increase in the value of couple stresses stabilize the system. The variable gravity can enhance or reduce the stability of the system depending on the direction of gravity variation which can be easily controlled by its parameter values. It is also observed that fluid confined in rigid-rigid bounding surface is more thermally stable, which is suitable for convection in couple stress fluid.

Nanomechanical collective vibration of SARS-CoV-2 spike proteins.

The development of effective therapeutics against COVID-19 requires a thorough understanding of the receptor recognition mechanism of the SARS-CoV-2 spike (S) protein. Here the multidomain collective dynamics on the trimer of the spike protein has been analyzed using normal mode analysis (NMA). A common nanomechanical profile was identified in the spike proteins of SARS-CoV-2 and its variants. The profile involves collective vibrations of the receptor-binding domain (RBD) and the N-terminal domain (NTD), which may mediate the physical interaction process. Quantitative analysis of the collective modes suggests a nanomechanical property involving large-scale conformational changes, which explains the difference in receptor binding affinity among different variants. These results support the use of intrinsic global dynamics as a valuable perspective for studying the allosteric and functional mechanisms of the S protein. This approach also provides a low-cost theoretical toolkit for screening potential pathogenic mutations and drug targets.

Designing a multi-epitope vaccine against Shigella dysenteriae using immuno-informatics approach.

Shigella dysenteriae has been recognized as the second most prevalent pathogen associated with diarrhea that contains blood, contributing to 12.9% of reported cases, and it is additionally responsible for approximately 200,000 deaths each year. Currently, there is no S. dysenteriae licensed vaccine. Multidrug resistance in all Shigella spp. is a growing concern. Current vaccines, such as O-polysaccharide (OPS) conjugates, are in clinical trials but are ineffective in children but protective in adults. Thus, innovative treatments and vaccines are needed to combat antibiotic resistance. In this study, we used immuno-informatics to design a new multiepitope vaccine and identified S. dysenteriae strain SD197's membrane protein targets using in-silico methods. The target protein was prioritized using membrane protein topology analysis to find membrane proteins. B and T-cell epitopes were predicted for vaccine formulation. The epitopes were shortlisted based on an IC50 value <50, antigenicity, allergenicity, and a toxicity analysis. In the final vaccine construct, a total of 8 B-cell epitopes, 12 MHC Class I epitopes, and 7 MHC Class II epitopes were identified for the Lipopolysaccharide export system permease protein LptF. Additionally, 17 MHC Class I epitopes and 14 MHC Class II epitopes were predicted for the Lipoprotein-releasing ABC transporter permease subunit LolE. These epitopes were selected and linked via KK, AAY, and GGGS linkers, respectively. To enhance the immunogenic response, RGD (arginine-glycine-aspartate) adjuvant was incorporated into the final vaccine construct. The refined vaccine structure exhibits a Ramachandran score of 91.5% and demonstrates stable interaction with TLR4. Normal Mode Analysis (NMA) reveals low eigenvalues (3.925996e-07), indicating steady and flexible molecular mobility of docked complexes. Codon optimization was carried out in an effective microbial expression system of the Escherichia coli K12 strain using the recombinant plasmid pET-28a (+). Finally, the entire in-silico analysis suggests that the suggested vaccine may induce a significant immune response against S. dysenteriae, making it a promising option for additional experimental trials.

Multifunctional in vitro, in silico and DFT analyses on antimicrobial BagremycinA biosynthesized by Micromonospora chokoriensis CR3 from Hieracium canadense

Among the actinomycetes in the rare genera, Micromonospora is of great interest since it has been shown to produce novel therapeutic compounds. Particular emphasis is now on its isolation from plants since its population from soil has been extensively explored. The strain CR3 was isolated as an endophyte from the roots of Hieracium canadense, and it was identified as Micromonospora chokoriensis through 16S gene sequencing and phylogenetic analysis. The in-vitro analysis of its extract revealed it to be active against the clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) and Candida tropicalis (15 mm). No bioactivity was observed against Gram-negative bacteria, Escherichia coli ATCC 25922, and Klebsiella pneumoniae ATCC 706003. The Micromonospora chokoriensis CR3 extract was also analyzed through the HPLC-DAD-UV–VIS resident database, and it gave a maximum match factor of 997.334 with the specialized metabolite BagremycinA (BagA). The in-silico analysis indicated that BagA strongly interacted with the active site residues of the sterol 14-α demethylase and thymidylate kinase enzymes, with the lowest binding energies of − 9.7 and − 8.3 kcal/mol, respectively. Furthermore, the normal mode analysis indicated that the interaction between these proteins and BagA was stable. The DFT quantum chemical properties depicted BagA to be reasonably reactive with a HOMO-LUMO gap of (ΔE) of 4.390 eV. BagA also passed the drug-likeness test with a synthetic accessibility score of 2.06, whereas Protox-II classified it as a class V toxicity compound with high LD50 of 2644 mg/kg. The current study reports an endophytic actinomycete, M. chokoriensis, associated with H. canadense producing the bioactive metabolite BagA with promising antimicrobial activity, which can be further modified and developed into a safe antimicrobial drug.

Radiation pressure and galactic cosmic rays-driven gravitational instability in rotating and magnetized viscoelastic fluids

This paper studies the combined effects of radiation and galactic cosmic ray pressures on the gravitational instability of magnetized and rotating viscoelastic fluids. The dispersion relations are derived using the normal mode analysis and discussed in the hydrodynamic (weakly coupled fluid) and kinetic (strongly coupled fluid) limits. These dispersion relations are analyzed separately for transverse and longitudinal wave propagation modes. Jeans instability criteria are obtained for kinetic and hydrodynamic limits for both modes of wave propagation, and it is found that the critical Jeans wavenumbers in each case are modified due to the presence of viscoelastic effects, radiation and cosmic rays pressures, and Alfvên wave velocity. It is also observed that the radiation pressure, cosmic ray pressure and viscoelastic parameters suppress the growth rate and thus have stabilizing effects on the Jeans instability. However, cosmic ray diffusion has a destabilizing effect on the onset of gravitational instability. The effects of various parameters on the growth rate of instability are calculated numerically and the outcomes are depicted graphically. The results of the present analysis shall be helpful in understanding the impact of cosmic rays and radiative mechanisms on the gravitational collapse in the viscoelastic region of molecular cloud clumps.

A Two-Temperature Nonlocal Poro-Thermoelastic Solid Via Higher-Order Time-Derivatives Model with Phase Lag

Abstract Purpose The present study has depicted the effect of gravitational on a two-temperature nonlocal poro-thermoelastic solid. Methods The multi-phase-lag model and fractional derivatives are used to tackle the issue. Through normal mode analysis, analytical formulas for the variable fields are derived. Using appropriate boundary conditions, the physical fields are calculated and the numerical computations have been carried out with the help of MATLAB programming. Results Through a careful comparison of the numerical data, the impacts of gravity, fractional derivative order, and locatiy on the behavior of physical fields are described. Conclusion Physical variables are affected by nonlocal thermoelasticity, fractional derivative order as well as the gravity field.

Response of Moisture and Temperature Diffusivity on an Orthotropic Hygro-thermo-piezo-elastic Medium

This research explores the complex interaction between piezoelectric waves and heat-moisture diffusion within a semi-infinite piezoelectric material under hygro-thermal conditions. By employing a two-dimensional Cartesian framework, novel governing equations for a thermo-piezoelectrically orthotropic medium influenced by moisture effects are developed. Accurate representations for key parameters are obtained by utilizing normal mode analysis. The investigation examines the influence of critical factors like moisture content, diffusivity, and temperature diffusivity on the spatial distribution of various physical fields. Additionally, a particular scenario of significance is highlighted. These results have the potential to improve sensor, actuator, and energy-harvesting device performance and dependability.

Stability of viscoelastic film on a slippery inclined plane

The linear and weakly nonlinear stability of viscoelastic film flowing down a slippery inclined plane is investigated analytically. Under the assumption of the long wave approximation, the first-order Benny equation of Oldroyd-B fluid thin film with slip condition is obtained. Through the normal mode analysis, the neutral stability curve and the temporal growth rates are calculated to explore the linear stability of the film. Linear results show that the critical Reynolds number decreases with the increase in slip length and viscoelastic parameter and that the liquid film may exhibit pure elastic instability. For the nonlinear stability analysis, both hydrodynamic instability and elastic instability are discussed. The primary bifurcations in the phase plane are identified by calculating the Landau coefficient, i.e., the unconditional stable region, the supercritical region, the subcritical region, and the explosive region. The dependence of primary bifurcation regions upon the slip length and Deborah number are studied, and the results indicate that the slip boundary and viscoelasticity destabilizes the flow. According to the Ginzburg–Landau equation, the threshold amplitude of the nonlinear equilibrium solution is analyzed as well.

Design and computational evaluation of a novel multi-epitope hybrid vaccine against monkeypox virus: Potential targets and immunogenicity assessment for pandemic preparedness

Monkeypox is a type of DNA-enveloped virus that belongs to the orthopoxvirus family, closely related to the smallpox virus. It can cause an infectious disease in humans known as monkeypox disease. Although there are multiple drugs and vaccines designed to combat orthopoxvirus infections, with a primary focus on smallpox, the recent spread of the monkeypox virus to over 50 countries have ignited a mounting global concern. This unchecked viral proliferation has raised apprehensions about the potential for a pandemic corresponding to the catastrophic impact of COVID-19. This investigation explored the structural proteins of monkeypox virus as potential candidates for designing a novel hybrid multi-epitope vaccine. The epitopes obtained from the selected proteins were screened to ensure their non-allergenicity, non-toxicity, and antigenicity to trigger T and B-cell responses. The interaction of the vaccine with toll-like receptor-3 (TLR-3) and major histocompatibility complexes (MHCs) was assessed using Cluspro 2.0. To establish the reliability of the docked complexes, a comprehensive evaluation was conducted using Immune and MD Simulations and Normal Mode Analysis. However, to validate the computational results of this study, additional in-vitro and in-vivo research is essential.

Dynamic response of a homogeneous hygrothermoelastic slab sandwiched between elastic half-spaces

In the current study, the authors discuss a homogeneous hygrothermoelastic slab of thickness 2h sandwiched between two similar elastic half-spaces. The hygrothermoelastic slab is subjected to a mechanical source of constant magnitude. The source is applied along the interface of the slab and upper elastic half-space. The analytical expressions of the components of displacement, stresses, moisture concentration, and temperature field are obtained by the normal mode analysis technique. The analytical results are used to solve the problem numerically by taking a wood slab as a porous material. The graphical results elaborate the effect of the thickness of a slab on the physical quantities. The problem of hygrothermoelastic layers sandwiched between elastic half-spaces is a novel idea, which finds its applications in various engineering models. The results found are interesting in the context of the problem. It is observed that the thickness of a hygrothermoelastic slab affects the deformation in the medium and the values of physical quantities decrease with an increase in the thickness of the slab.

Chiral Spectroscopy of Bulk Systems with Propagated Localized Orbitals.

We present approaches for the simulation of electronic circular dichroism, Raman, and Raman optical activity (ROA) spectra for isolated and periodic systems as well as subsystem analysis thereof. The method is based on the use of time-dependent maximally localized Wannier functions in the CP2K package and accounts for origin dependencies inherent to the Gaussian and plane wave with pseudopotentials approach as well as the origin dependence of the magnetic dipole and electric quadrupole operators. Tests on the H-bonded enantiomers of alanine by harmonic normal-mode analysis and on an aqueous solution of l-alanine by ab initio molecular dynamics obeying periodic boundary conditions (PBCs) are presented as total and subsystem-resolved spectra. To our knowledge, this is the first instance of an ROA spectrum derived from real-time propagation obeying PBCs and the first ROA simulation considering off-, pre-, and on-resonance effects within PBCs.

Scalable computation of anisotropic vibrations for large macromolecular assemblies

The Normal Mode Analysis (NMA) is a standard approach to elucidate the anisotropic vibrations of macromolecules at their folded states, where low-frequency collective motions can reveal rearrangements of domains and changes in the exposed surface of macromolecules. Recent advances in structural biology have enabled the resolution of megascale macromolecules with millions of atoms. However, the calculation of their vibrational modes remains elusive due to the prohibitive cost associated with constructing and diagonalizing the underlying eigenproblem and the current approaches to NMA are not readily adaptable for efficient parallel computing on graphic processing unit (GPU). Here, we present eigenproblem construction and diagonalization approach that implements level-structure bandwidth-reducing algorithms to transform the sparse computation in NMA to a globally-sparse-yet-locally-dense computation, allowing batched tensor products to be most efficiently executed on GPU. We map, optimize, and compare several low-complexity Krylov-subspace eigensolvers, supplemented by techniques such as Chebyshev filtering, sum decomposition, external explicit deflation and shift-and-inverse, to allow fast GPU-resident calculations. The method allows accurate calculation of the first 1000 vibrational modes of some largest structures in PDB ( > 2.4 million atoms) at least 250 times faster than existing methods.

Polytropic spherical astrocosmic fluid stability in the EiBI gravity with strong collective correlative effects

We herein present a dynamical analysis of the Jeans (gravitational) instability in a viscoelastic polytropic astrocloud within the Eddington-inspired Born-Infeld (EiBI) gravity framework in spherical geometry. The zeroth-order material density curvature corrections to the effective self-gravitational potential are properly incorporated. The applied spherical normal mode analysis yields a unique form of monic cubic dispersion relation with multiparametric coefficients dependent on the diverse equilibrium astrofluidic conditions without invoking any kind of traditional quasi-classic approximation. It is seen that the positive EiBI gravity parameter (χ>0) acts as a stabilizing agent and a negative EiBI gravity parameter (χ<0) acts as a destabilizing agent against the inward non-local self-gravity action. Additionally, we find that larger astroclouds are more prone to gravitational collapse, irrespective of the χ-polarity, and vice-versa. It is further investigated that the cloud temperature plays a stabilizing role at larger wavenumbers and destabilizing at smaller wavenumbers for χ>0. However, for χ<0, the fluid temperature consistently exhibits a destabilizing effect. The viscoelastic relaxation time stabilizes the astrofluid against the self-gravity irrespective of the χ-polarity. The fluid density acts as a stabilizer for χ>0, destabilizer for χ<0, and so forth. This study could be potentially applicable in the EiBI-modified gravitational theory in exploring gravity-driven large-scale astrocosmic phenomena towards structure formation mechanism via the canonical Jeans condensation in diverse astrocosmic conditions.

A Fresh Look at the Normal Mode Analysis of Proteins: Introducing Allosteric Co-Vibrational Modes.

We propose a new way of utilizing normal modes to study protein conformational transitions. Instead of considering individual modes independently, we show that a weighted mixture of low-frequency vibrational modes can reveal dynamic information about the conformational mechanism in more detail than any single mode can. The weights in the mixed mode, termed the allosteric covibrational mode, are determined using a simple model where the conformational transition is viewed as a perturbation of the coupled harmonic oscillator associated with either of the two conformations. We demonstrate our theory in a biologically relevant example of high pharmaceutical interest involving the V617F mutation of Janus 2 tyrosine kinase (JAK2).

Pan-cancer analyses suggest kindlin-associated global mechanochemical alterations

Kindlins serve as mechanosensitive adapters, transducing extracellular mechanical cues to intracellular biochemical signals and thus, their perturbations potentially lead to cancer progressions. Despite the kindlin involvement in tumor development, understanding their genetic and mechanochemical characteristics across different cancers remains elusive. Here, we thoroughly examined genetic alterations in kindlins across more than 10,000 patients with 33 cancer types. Our findings reveal cancer-specific alterations, particularly prevalent in advanced tumor stage and during metastatic onset. We observed a significant co-alteration between kindlins and mechanochemical proteome in various tumors through the activation of cancer-related pathways and adverse survival outcomes. Leveraging normal mode analysis, we predicted structural consequences of cancer-specific kindlin mutations, highlighting potential impacts on stability and downstream signaling pathways. Our study unraveled alterations in epithelial–mesenchymal transition markers associated with kindlin activity. This comprehensive analysis provides a resource for guiding future mechanistic investigations and therapeutic strategies targeting the roles of kindlins in cancer treatment.

Thermoelastic diffusion in nonlocal orthotropic medium with porosity

The present article investigates the linear theory of nonlocal thermoelasticity in homogeneous orthotropic porous medium with diffusion in the context of dual-phase-lag model. The focal point of the present study involves an examination of Fick’s mass diffusion law and the generalized Fourier’s law within the context of the dual-phase-lag model of hyperbolic thermoelasticity. The incorporation of voids, mass diffusion with phase lagging in the diffusion flux is the basis for establishing the void diffusion-elasticity models. Furthermore, the new dual-phase-lag diffusion model introduces the consideration of nonlocal effects in mass transfer. The resolution of the problem involves the utilization of normal mode analysis, employed for solving, and encompasses the application of thermal shock at the surface boundary. Numerical calculations of stress components, displacement components, voids, temperature, and concentration of the diffusive material are performed for various distances and time intervals.

Stability analysis of thermosolutal convection in a rotating Navier–Stokes–Voigt fluid

Abstract This work presents nonlinear and linear analyses of the rotating Navier–Stokes–Voigt fluid layer that is simultaneously heated and soluted from below, considering different boundary surfaces. The energy method is used to form the eigenvalue problem for nonlinear analysis, whereas the normal mode analysis is used for the linear analysis. The Rayleigh number is numerically calculated by employing the Galerkin technique. Both nonlinear and linear analyses yield the same Rayleigh number, indicating the absence of subcritical regions and implying global stability. The Kelvin–Voigt parameter doesn’t affect the Rayleigh number for stationary convection. However, the crucial role of this parameter is established through an energy argument. The presence of rotation, Kelvin–Voigt parameter, and solute gradient give rise to oscillatory modes. Also, the effects of rotation and solute gradient are stabilizing on the system, whereas the stabilizing effect of the Kelvin–Voigt parameter becomes evident when convection exhibits an oscillatory behavior.