Radius Of Gyration Research Articles

Hemoglobin-PEG Interactions Probed by Small-Angle X-ray Scattering: Insights for Crystallization and Diagnostics Applications.

Protein-protein interactions, controlling protein aggregation in the solution phase, are crucial for the formulation of protein therapeutics and the use of proteins in diagnostic applications. Additives in the solution phase are factors that may enhance the protein's conformational stability or induce crystallization. Protein-PEG interactions do not always stabilize the native protein structure. Structural information is needed to validate excipients for protein stabilization in the development of protein therapeutics or use proteins in diagnostic assays. The present study investigates the impact of polyethylene glycol (PEG) molecular weight and concentration on the spatial structure of human hemoglobin (Hb) at neutral pH. Small-angle X-ray scattering (SAXS) in combination with size-exclusion chromatography is employed to characterize the Hb structure in solution without and with the addition of PEG. Our results evidence that human hemoglobin maintains a tetrameric conformation at neutral pH. The dummy atom model, reconstructed from the SAXS data, aligns closely with the known crystallographic structure of methemoglobin (metHb) from the Protein Data Bank. We established that the addition of short-chain PEG600, at concentrations of up to 10% (w/v), acts as a stabilizer for hemoglobin, preserving its spatial structure without significant alterations. By contrast, 5% (w/v) PEG with higher molecular weights of 2000 and 4000 leads to a slight reduction in the maximum particle dimension (Dmax), while the radius of gyration (Rg) remains essentially unchanged. This implies a reduced hydration shell around the protein due to the dehydrating effect of longer PEG chains. At a concentration of 10% (w/v), PEG2000 interacts with Hb to form a complex that does not distort the protein's spatial configuration. The obtained results provide a deeper understanding of PEG's influence on the Hb structure in solution and broader knowledge regarding protein-PEG interactions.

In silico analysis reveals α-amylase inhibitory potential of Taraxerol (Coccinia indica) and Epoxywithanolide-1 (Withania coagulans): a possible way to control postprandial hyperglycemia-induced endothelial dysfunction and cardiovascular events.

Postprandial hyperglycemia (PPG) exacerbates endothelial dysfunction and impairs vascular function in diabetes as well in healthy people. Though synthetic drugs are available to regulate PPG, the severe gastrointestinal side effects of those medications have prompted the search for alternative treatments. Recently, some phytochemicals captured the attention because of their inhibitory effects on α-amylase to control diabetes. The aim of this study was to investigate and identify potential alpha-amylase inhibitors in C. indica and W. coagulans. This study also aims to understand one of the possible mechanisms of action of plants for their anti-diabetic activity. A total of 36 phytochemical ligands were subjected for protein-ligand docking analysis. Among the phytochemicals, Taraxerol and Epoxywithanolide-I demonstrated significant binding free energy of -10.2kcal/mol and -11.9kcal/mol respectively, which was higher than the reference acarbose with -8.6kcal/mol. These molecules were subjected for molecular dynamics simulation (MDS) analysis with alpha-amylase protein for a duration of 150ns. Among the three complexes, Taraxerol and Epoxywithanolide-I complexes demonstrates strong potential as inhibitors of the target protein. MDS results were analyzed via root mean square deviation (RMSD), fluctuation of residues, potential energy, radii of gyration and solvent access surface area analysis. Taraxerol demonstrated a significantly low potential energy of -1,924,605.25kJ/mol, and Epoxywithanolide-I demonstrated -1,964,113.3kJ/mol of potential energy. RMSD plot shows that Epoxywithanolide-I has much higher stability than the other MDS complexes. Drugability and toxicity studies show that the test ligands are demonstrating strong potential as drug like molecules. The results of the study conclude that, Taraxerol of C. indica and Epoxywithanolide-I of W. coagulans are strong inhibitors of alpha-amylase enzyme and that, this is one of the possible mechanisms of action of the plants for their reported anti-diabetic activities. Further in-vitro analysis is in demand to prove the observed results.

Early Events in G-quadruplex Folding Captured by Time-Resolved Small-Angle X-Ray Scattering.

Time-resolved small-angle X-ray experiments (TR-SAXS) are reported here that capture and quantify a previously unknown rapid collapse of the unfolded oligonucleotide as an early step in G4 folding of hybrid 1 and hybrid 2 telomeric G-quadruplex structures. The rapid collapse, initiated by a pH jump, is characterized by an exponential decrease in the radius of gyration from 20.6 to 12.6 Å. The collapse is monophasic and is complete in less than 600 ms. Additional hand-mixing pH-jump kinetic studies show that slower kinetic steps follow the collapse. The folded and unfolded states at equilibrium were further characterized by SAXS studies and other biophysical tools, to show that G4 unfolding was complete at alkaline pH, but not in LiCl solution as is often claimed. The SAXS Ensemble Optimization Method (EOM) analysis reveals models of the unfolded state as a dynamic ensemble of flexible oligonucleotide chains with a variety of transient hairpin structures. These results suggest a G4 folding pathway in which a rapid collapse, analogous to molten globule formation seen in proteins, is followed by a confined conformational search within the collapsed particle to form the native contacts ultimately found in the stable folded form.

Analytical and Numerical Investigation of Star Polymers in Confined Geometries.

The analysis of the impact of the star polymer topology on depletion interaction potentials, depletion forces, and monomer density profiles is carried out analytically using field theory methods and techniques as well as molecular dynamic simulations. The dimensionless depletion interaction potentials and the dimensionless depletion forces for a dilute solution of ideal star polymers with three and five legs (arms) in a Θ-solvent confined in a slit between two parallel walls with repulsive surfaces and for the case where one of the surfaces is repulsive and the other inert are obtained. Furthermore, the dimensionless layer monomer density profiles for ideal star polymers with an odd number (f˜ = 3, 5) of arms immersed in a dilute solution of big colloidal particles with different adsorbing or repelling properties in respect of polymers are calculated, bearing in mind the Derjaguin approximation. Molecular dynamic simulations of a dilute solution of star-shaped polymers in a good solvent with N = 901 (3 × 300 + 1 -star polymer with three arms) and 1501 (5 × 300 + 1 -star polymer with five arms) beads accordingly confined in a slit with different boundary conditions are performed, and the results of the monomer density profiles for the above-mentioned cases are obtained. The numerical calculation of the radius of gyration for star polymers with f˜ = 3, 5 arms and the ratio of the perpendicular to parallel components of the radius of gyration with respect to the wall orientation for the above-mentioned cases is performed. The obtained analytical and numerical results for star polymers with an odd number (f˜ = 3, 5) of arms are compared with our previous results for linear polymers in confined geometries. The acquired results show that a dilute solution of star polymer chains can be applied in the production of new functional materials, because the behavior of these solutions is strictly correlated with the topology of polymers and also with the nature and geometry of confined surfaces. The above-mentioned properties can find extensive practical application in materials engineering, as well as in biotechnology and medicine for drug and gene transmission.

Molecular analysis of changes in DNA binding affinity and bending extent induced by the mutations on the aromatic amino residues in Cren7.

Proteins from Crenarchaeal organisms exhibit remarkable thermal stability. The aromatic amino acids in Cren7, a Crenarchaeal protein, regulate protein stability and further modulate DNA binding and its compaction. Specific aromatic amino acids were mutated, and using spectroscopic and theoretical approaches, we have examined the structure, DNA binding affinity, and DNA bending ability of mutants. and compared with wild-type (WT) Cren7. The reverse titration profiles were analysed by a noncooperativeMcGhee-von Hippel model to estimate affinity constant (Ka) and site size (n) associated with binding to the DNA. Biolayer interferometry (BLI) measurements showed that the binding affinity decreased at higher salt concentrations. For theoretical analysis of extent of DNA bending, radius of gyration and bending angle were compared for WT and mutants. Time evolution of order parameters based on translational and rotational motion of tryptophan residue (W26) was used for qualitative detection of stacking interactions between W26 of Cren7 and DNA nucleobases. It was observed that orientation of W26 in F41A favoredformation of a new lone pair-lone pair interaction between DNA and Cren7. Consequently, in thermostable proteins, the aromatic residues at the terminus maintain structural stability, whereas the residues at the core optimize the degree of DNA bending and compaction.

Exploring the potential of Scabiosa columbaria in Alzheimer's disease treatment: An in silico approach

ObjectivesAlzheimer's disease (AD) is posing an increasing global threat and currently lacks effective treatments. Therefore, this study was aimed at exploring phytochemicals in Scabiosa columbaria (S. columbaria) as inhibitors of acetylcholinesterase (AChE), β-site APP cleavage enzyme 1 (BACE1), and TNF-α converting enzyme (TACE) in AD. S. columbaria contains various bioactive compounds, such as chlorogenic acid, linalool, and catechins, which are known for their detoxification properties, capacity to resist and manage harmful moisture buildup, and therapeutic roles in COVID-19. Several studies have also shown that S. columbaria extract has strong antioxidant activity, and may potentially decrease neuroinflammation in AD. Therefore, this study investigated the interactions between S. columbaria phytochemicals and key enzymes associated with AD, thus providing opportunities for the development of new therapeutic candidates. MethodsA total of 27 phytochemicals were evaluated for their inhibitory activity against AChE, BACE1, and TACE with YASARA Structure. ADMET profiles and toxicity were assessed. The top candidate compounds underwent 100 ns MD simulations. ResultsAll ligands met Lipinski's rule and showed low toxicity. Catechins, compared with the known drug galantamine, showed higher inhibitory activity and interacted with additional active sites on AChE, thus suggesting potentially higher efficacy. Moreover, chlorogenic acid showed stronger inhibitory activity against TACE than the control drug (aryl-sulfonamide), thereby suggesting a different mechanism of action. MD simulation revealed that the formed complexes had good stability. However, further exploration is necessary. ConclusionS. columbaria derivative compounds are promising drug candidates because of their properties, including the affinity of chlorogenic acid toward TACE and hydrogen bond enhancing ligand–receptor interactions. MD simulation indicated stable ligand–protein complexes, and the radius of gyration and MM-PBSA calculations revealed favorable binding and interaction energies. Our findings demonstrate the identified compounds' potential for further drug development.

An integrative characterization of proline cis and trans conformers in a disordered peptide

Intrinsically disordered proteins (IDPs) often contain proline residues that undergo cis/trans isomerization. While molecular dynamics (MD) simulations have the potential to fully characterize the proline cis and trans subensembles, they are limited by the slow timescales of isomerization and force field inaccuracies. NMR spectroscopy can report on ensemble-averaged observables for both the cis-proline and trans-proline states, but a full atomistic characterization of these conformers is challenging. Given the importance of proline cis/trans isomerization for influencing the conformational sampling of disordered proteins, we employed a combination of all-atom MD simulations with enhanced sampling (metadynamics), NMR, and small-angle x-ray scattering (SAXS) to characterize the two subensembles of the ORF6 C-terminal region (ORF6CTR) from SARS-CoV-2 corresponding to the proline-57 (P57) cis and trans states. We performed MD simulations in three distinct force fields: AMBER03ws, AMBER99SB-disp, and CHARMM36m, which are all optimized for disordered proteins. Each simulation was run for an accumulated time of 180–220 μs until convergence was reached, as assessed by blocking analysis. A good agreement between the cis-P57 populations predicted from metadynamic simulations in AMBER03ws was observed with populations obtained from experimental NMR data. Moreover, we observed good agreement between the radius of gyration predicted from the metadynamic simulations in AMBER03ws and that measured using SAXS. Our findings suggest that both the cis-P57 and trans-P57 conformations of ORF6CTR are extremely dynamic and that interdisciplinary approaches combining both multiscale computations and experiments offer avenues to explore highly dynamic states that cannot be reliably characterized by either approach in isolation.

On the use of dioxane as reference for determination of the hydrodynamic radius by NMR spectroscopy

Measuring the compaction of a protein or complex is key to our understanding of the interactions within and between biomolecules. Experimentally, protein compaction is often probed either by estimating the radius of gyration (Rg) obtained from small-angle x-ray scattering (SAXS) experiments or the hydrodynamic radius (Rh) obtained, for example, by pulsed field gradient NMR (PFG NMR) spectroscopy. PFG NMR experiments generally report on the translational diffusion coefficient, which in turn can be used to estimate Rh using an internal standard to account for sample viscosity and uncertainty about the gradient strength. 1,4-Dioxane is one such commonly used internal standard, and the reference value of Rh is therefore important. We have revisited the basis for the commonly used reference value for the Rh of dioxane (2.12 Å) that is used to convert measured diffusion coefficients into a hydrodynamic radius. We followed the same approach that was used to establish the current reference value by measuring SAXS and PFG NMR data for a set of seven different proteins and using these as standards. Our analysis shows that the current Rh reference value for dioxane Rh is underestimated, and we instead suggest a new value of 2.27 ± 0.04 Å. Using this updated reference value results in a ∼7% increase in Rh values for proteins whose hydrodynamic radii have been measured by PFG NMR. These results are particularly important when the absolute value of Rh is of interest such as when determining or validating ensemble descriptions of intrinsically disordered proteins.

Orientation of Linear Liquid Alkane on Solid Surface of Face Centered Cubic Lattice of (100), (110) and (111)

Solid-liquid (S-L) interfaces are found in numerous engineering applications, such as lubrication and coating systems as well as thermal interface materials. Understanding the interactions between (S-L) is crucial for optimizing various engineering applications. The main objective of this study is to provide insight regarding liquid adsorption on solid surfaces using non-equilibrium molecular dynamics simulations. To achieve this goal, a liquid confined between solid surfaces will be modeled to match the real state of contact interfaces using a constant temperature as a baseline. The results highlight a significant relationship between the peak height values of the liquid adsorption layer, density profile, and radius of gyration. Specifically, the peak height density at the S-L interfaces for the crystal plane (110) is 784.756 kg/m3, followed by (100) at 801.786 kg/m3, and finally the highest is for the crystal plane (111), at 966.940 kg/m3. Whereas the radius of gyration at the S-L interfaces for crystal planes (100) and (111) is approximately 7.45 × 10-21 m2, but for crystal plane (110) it is less and measures approximately 7.06 × 10-21 m2. Conclusion, the adsorption layer of solid density near solid-liquid interfaces is significantly influenced by the peak height of the solid's density. Higher density results in a higher adsorption layer of liquid near solid-liquid interfaces. The number of solid density layers does not affect the height of adsorption layers for liquids.

Combination of ligand‑based and structure‑based virtual screening for the discovery of novel Janus kinase 2 inhibitors against philadelphia-negative myeloproliferative neoplasms.

The activating V617F mutation in Janus kinase 2 (JAK2) has been shown to be the major cause for classic Philadelphia-negative myeloproliferative neoplasms (MPNs). Thus, the development of pharmacologic JAK2 inhibitors is an essential move in combating MPNs. In this study, screening methods examining both ligands and their structures were developed to discover novel JAK2 inhibitors from the ChemDiv database with virtual screening identifying 886 candidate inhibitors. Next, these compounds were further filtered using ADMET, drug likeliness, and PAINS filtering, which reduced the compound number even further. This consolidated list of candidate compounds (n = 49) was then evaluated biologically at molecular level and the highest performing inhibitor with a novel scaffold was selected for further examination. This candidate inhibitor, CD4, was then subjected to molecular dynamics studies, with complex stability, root-mean-square deviation, radius of gyration, binding free energy, and binding properties all examined. The result suggested that CD4 interacts with JAK2 and that the CD4-JAK2 complex is stable. This study was able to identify a candidate inhibitor that warrants further examination and optimization and may potentially serve as a future MPN treatment.

Optimized Collective Variable for Collapse Transition in Linear Hydrophobic Polymers: Importance of Hydration Water and End-to-End Distance.

Choosing an appropriate collective variable (CV) for any biomolecular process is a challenging task. Researchers are developing methods to solve this issue using a variety of methodologies, most recently using machine learning (ML) methods. In this work, we investigate the mechanism of collapse transition across various lengths of polymer systems through adaptively sampled multiple short trajectories utilizing the Time Lagged Independent Component Analysis (TICA) framework. From TICA analysis, it is revealed that the radius of gyration (Rg) and end-to-end distance serve as good order parameters (OPs) for these systems describing overall energy landscapes. Markov state model (MSM) and mean first passage time (MFPT) analysis suggest that hydration water (Nw) plays a determining role in dictating the time scale and barrier for the collapsed transition for the C40 system. P-fold analysis on identifying transition state ensembles (TSE) identified by committor analysis also strengthens the role of Nw in such a transition. TICA, MSM, and committor analyses on the collapse transition for C45 reveal similarities with C40 systems in different aspects. Furthermore, we propose a pipeline integrating XGBoost regression along with an interpretable ML model, Shapley Additive exPlanation (SHAP) to precisely elucidate the contribution of each OP locally at the TSE. Through this approach, we observe that the collapse transition is primarily driven by Nw for both polymer systems. A carefully designed protocol for the collapsed transition of C60 systems indirectly reiterates the above result. Overall, our results suggest that while the end-to-end distance should be considered for better resolution of metastable states in the landscape, Nw is the crucial coordinate to be used in enhanced sampling for the exploration of actual collapse transitions for linear hydrophobic polymer systems. The Python code for analyzing the contribution of different OPs in the TSE using an ML-aided protocol is available on GitHub (https://github.com/saikat-ai/linear_polymer_project).

Identification of small molecule glucokinase activators for the treatment of diabetes based on plants from the traditional Chinese medicine: In silico analysis

Mutations in glucokinase (GCK) can either enhance or inhibit insulin secretion, leading to different forms of diabetes, including gestational diabetes. While many glucokinase activators (GKAs) have been explored as treatments, their long-term effectiveness has often been unsatisfactory. However, recent interest has surged with the introduction of dorzagliatin and TTP399. This study investigates the efficacy of four previously studied compounds (Swertiamarin, Apigenin, Mangiferin, and Tatanan A) in activating GCK using computational methods.Initial molecular docking revealed binding affinities ranging from −6.7 to −8.6 kcal/mol. The compounds were then evaluated for drug-likeness and pharmacokinetic properties. Re-docking studies were performed for validation. Based on their favorable binding affinities and compliance with Lipinski's rule and ADMET criteria, three compounds (Swertiamarin, Apigenin, and Tatanan A) were selected for molecular dynamics (MD) simulations.MD simulations demonstrated that Swertiamarin showed excellent stability, as indicated by analyses of RMSD, RMSF, radius of gyration (Rg), hydrogen bonding, and principal component analysis (PCA). These results suggest that Swertiamarin holds promise for further investigation in in vivo and clinical settings to evaluate its potential in enhancing GCK activity and treating diabetes.This study assessed the potential of four compounds as GCK activators using molecular docking, pharmacokinetic profiling, and MD simulations. Swertiamarin, in particular, showed significant stability and adherence to drug-likeness criteria, making it a promising candidate for further research in combating diabetes.

The Study of Molecular Docking and Molecular Dynamics Simulation Chemical Compound of Pycnarrhena cauliflora Diels. as Proapoptosis in Cervical Cancer

Cervical cancer is one of the most common cancers among women worldwide and in Indonesia. B-cell lymphoma 2 (Bcl-2) can play a role in causing cancer by inhibiting apoptosis. The purpose of this study was to analyze the chemical compound of the sengkubak plant (Pycnarrhena cauliflora Diels.), which can act as antiapoptotic inhibitor by binding to the B-cell lymphoma 2 (Bcl-2) receptor. The research was conducted in silico with molecular docking methods and molecular dynamics simulations. Molecular docking used the AutoDock 4.2.6 software and visualization used Biovia Discovery Studio. Molecular dynamics simulation used Gromacs 5.1.2 software and result visualization used Grace. Longipinocarvone was the best test ligand with the smallest ΔGbind value of -6.99 kcal/mol compared to the positive control of Doxorubicin and other compounds which indicating Longipinocarvone’s affinity for binding to the Bcl-2 receptor was better than Doxorubicin. The types of interactions involved in the molecular docking of the chemical compounds of the sengkubak plant and Doxorubicin including hydrogen bonds and hydrophobic interactions. The stability of the bond between the ligand protein complex resulting from molecular docking was analyzed based on the parameters RMSD, RMSF, Radius of Gyration (Rg) values through molecular dynamics simulations. The results of the analysis showed that Longipinocarvone and Doxorubicin had a stable bond with Bcl-2 as indicated by the RMSD and RMSF values meeting the requirements, namely <3 Å (0.3 nm). The Rg graph showed both complexes are stable during simulation and have resemblant ligand-protein movements.Keywords: Cervical cancer, B-cell lymphoma 2 (Bcl-2), Pycnarrhena cauliflora Diels., molecular docking, molecular dynamics.

Insights into the mechanism of crotamine and potential targets involved in obesity-related metabolic pathways

Crotamine (Ctm) is a peptide isolated from Crotalus durissus terrificus venom. This molecule has been demonstrated to diminish body weight gain and enhance browning in adipose tissue, glucose tolerance, and insulin sensitivity; hence, it has been postulated as an anti-obesogenic peptide. However, the mechanism to elicit the anti-obesogenic effects has yet to be elucidated. Thus, we investigated the possible interaction of Ctm with receptors involved in obesity-related metabolic pathways through protein-protein docking and molecular dynamics refinement. To test the anti-obesogenic mechanism of Ctm, we selected and retrieved 18 targets involved in obesity-related drug discovery from Protein Data Bank. Then, we performed protein-protein dockings. The best three Ctm-target models were selected and refined by molecular dynamics simulations. Molecular docking demonstrated that Ctm was able to interact with 13 of the 18 targets tested. Having a better docking score with glucagon-like peptide-1 receptor (GLP-1R) (−1430.2 kcal/mol), DPP-IV (dipeptidyl peptidase-IV) (−1781.7 kcal/mol) and α-glucosidase (−1232.3 kcal/mol). These three models were refined by molecular dynamics. Ctm demonstrated a higher affinity for GLP-1R (ΔG: −41.886 ± 2.289 kcal/mol). However, Ctm interaction was more stable with DPP-IV (RMSD: 0.360 ± 0.015 nm, Radius of gyration: 2.781 ± 0.009 nm). Moreover, the number of interactions and the molecular mechanics energies of Ctm residues suggest that the interaction of Ctm with these receptors is mainly mediated by basic-hydrophobic dyads Y1-K2, W31-R32, and W33-R34. Together, all these results allow elucidating a possible molecular mechanism behind the previously described anti-obesogenic effects.

Structure identification and activity evaluation of polysaccharide from Codonopsis pilosula (C. pilosula nannf. Var. modesta (nannf.) L. T. Shen)

Codonopsis pilosula is a medicinal plant with properties related to food, and the antioxidant and hypoglycemic components of its natural polysaccharides, as well as their related mechanisms, have not been fully understood. This study examined the physicochemical properties and structure of C. pilosula polysaccharide (WCP) using an orthogonal extraction method involving hot water-alcohol precipitation, high-resolution spectroscopy, and microscopic imaging technology. The antioxidant and hypoglycemic activities of the polysaccharides were assessed. Six fractions (WCP1, WCP2, WCP3, WCP4, WCP5, and WCP6) were identified through purification using a DEAE-cellulose column and Sephadex G-100 gel column. Mannose, glucose, and arabinose were identified as the primary monosaccharide components of WCPs through Gas Chromatography (GC). The polysaccharide exhibited a crystal structure composed of irregularly entangled pyranose particles of WCPs as revealed by X-ray diffraction (XRD), scanning electron microscopy (SEM), and atomic force microscopy (AFM). The polysaccharide decomposed into smoother triple-helix fibrous flocs as indicated by Congo red analysis and circular dichroism analysis (CD). The antioxidant capacity of the polysaccharides against various free radicals was evaluated, with WCP4 demonstrating a significant reducing capacity. Moreover, WCP3 and WCP5 displayed notable inhibition rates of α-amylase and α-glucosidase, respectively. Molecular docking studies indicated the interaction of WCP5 with two enzymes, forming multiple hydrogen bonds through specific amino acids. In the gromacs simulation, both composite systems maintained a steady state in terms of root mean square deviation (RMSD), root mean square fluctuation (RMSF), and radius of gyration, providing strong support for their potential as a reference for the developing novel therapeutic approaches to diabetes.

In-silico binding affinity of a phage display library screened novel peptide against various FABPs.

In accordance to the American Heart Association (AHA), cardiovascular diseases (CVDs) are the leading cause of death around the globe, causing more than 19.1million deaths in 2020. Heart-type fatty acid binding protein (H-FABP) is required for the metabolism of fatty acids (FA) inside cardiomyocytes is reported as a biomarker for myocardial damage. As early as one hour after an Acute myocardial infarction (AMI), H-FABP can be used to detect myocardial ischemia. Thus, H-FABP based detection can reduce the burden on the emergency department. A peptide-based detection system can provide point-of-care diagnostics for CVDs. There is a lot of research being done on peptide-based detection, and it has a lot of potential to help with unmet medical diagnostic needs. A twelve (12) amino acid peptide has been discovered using Phage Display Library Screening. The affinity of peptide with H-FABP and other FABPs has been done using molecular docking and ADMET profile has been done. Molecular docking of small peptides against the target protein can play a crucial role in recognizing peptide binding sites and poses. The docking study was done using the HDOCK server and the visualization of the docked complex was done using Pymol and UCSF chimera. The molecular simulation study of three protein-peptide complexes were done which also validated the binding affinity of peptide with the proteins. The RMSD, RMSF and radius of gyration are also analyzed. The results indicate that H-FABP shows higher level of binding interaction with the peptide having bond length ranging from 2.3 to 3.4 Å. The screened peptide is suitable for H-FABP binding and can be used for prognosis purposes in the heart ischemic conditions.

Numerical Study on the Effect of Weight Variables on the Roll Damping Coefficients for a Fishing Vessel

Abstract The roll damping coefficient is essential when considering the viscous effect in the potential-based hydrodynamic analysis of fishing vessels; it is an important factor in the roll motion response. The present study performs free roll decay simulations, altering weight variables using Computational Fluid Dynamics (CFD) to investigate the correlation between the roll damping coefficient and the weight variation of a fishing vessel. The time series of roll amplitude and roll damping coefficient are compared, for varying vertical and longitudinal centres of gravity and radii of gyration in roll motion. As the vertical centre of gravity increases, both the roll decay period and the roll damping coefficient also increase. The roll decay period tends to increase with the increase in the radius of gyration during roll motion, while the roll damping coefficient exhibits a decrease. A longitudinal centre of gravity has a limited effect on free roll decay characteristics. The roll damping coefficients between the maximum and minimum combinations of weight variables show significant differences. The findings of the present study could enhance the understanding of the safety of fishing vessels based on their loading conditions. Consequently, future research could further improve the results obtained in the present study by considering various hull shapes and speeds.

Expression, Purification, and Evaluation of Antibody Responses and Antibody-Immunogen Complex Simulation of a Designed Multi-Epitope Vaccine against SARS-COV-2.

The spread of the COVID-19 disease is the result of an infection caused by the SARS-CoV2 virus. Four crucial proteins, spike [S], membrane [M], nucleocapsid [N], and envelope [E] in coronaviruses have been considered to a large extent. This research aimed to express the recombinant protein of a multiepitope immunogen construct and evaluate the immunogenicity of the multiepitope vaccine that was previously designed as a candidate immunogenic against SARS-Cov-2. Plasmid pET26b was transferred to the expression host E. coli BL21 [DE3] and the recombinant protein was expressed with IPTG induction. The recombinant protein was purified by Ni-NTA column affinity chromatography, and western blotting was used to confirm it. Finally, mice were immunized with recombinant protein in three doses. Then, the interaction of the 3D structure of the vaccine with the human neutralizing antibodies3D structures [7BWJ and 7K8N] antibody was evaluated by docking and molecular dynamics simulation. The optimized gene had a codon compatibility index of 0.96. The expression of the recombinant protein of the SARS-Cov-2 vaccine in an E. coli host led to the production of the recombinant protein with a weight of about 70 kDa with a concentration of 0.7 mg/ml. Immunization of mice with recombinant protein of SARS-Cov-2 vaccine-induced IgG serum antibody response. Statistical analysis showed that the antibody titer in comparison with the control sample has a significant difference, and the antibody titer was acceptable up to 1/256000 dilution. The simulation of vaccine binding with human antibodies by molecular dynamics showed that Root Mean Square Deviation [RMSD], Root Mean Square Fluctuation [RMSF], Radius of Gyration, and H-bond as well as van der Waals energies and electrostatic of Molecular mechanics Poisson- Boltzmann surface area [MM/PBSA] analysis have stable interaction. This recombinant protein can probably be used as an immunogen candidate for the development of vaccines against SARS-CoV2 in future research.

Design and Optimization of Molecularly Imprinted Polymer Targeting Epinephrine Molecule: A Theoretical Approach.

Molecularly imprinted polymers (MIPs) are a growing highlight in polymer chemistry. They are chemically and thermally stable, may be used in a variety of environments, and fulfill a wide range of applications. Computer-aided studies of MIPs often involve the use of computational techniques to design, analyze, and optimize the production of MIPs. Limited information is available on the computational study of interactions between the epinephrine (EPI) MIP and its target molecule. A rational design for EPI-MIP preparation was performed in this study. First, density functional theory (DFT) and molecular dynamic (MD) simulation were used for the screening of functional monomers suitable for the design of MIPs of EPI in the presence of a crosslinker and a solvent environment. Among the tested functional monomers, acrylic acid (AA) was the most appropriate monomer for EPI-MIP formulation. The trends observed for five out of six DFT functionals assessed confirmed AA as the suitable monomer. The theoretical optimal molar ratio was 1:4 EPI:AA in the presence of ethylene glycol dimethacrylate (EGDMA) and acetonitrile. The effect of temperature was analyzed at this ratio of EPI:AA on mean square displacement, X-ray diffraction, density distribution, specific volume, radius of gyration, and equilibrium energies. The stability observed for all these parameters is much better, ranging from 338 to 353 K. This temperature may determine the processing and operating temperature range of EPI-MIP development using AA as a functional monomer. For cost-effectiveness and to reduce time used to prepare MIPs in the laboratory, these results could serve as a useful template for designing and developing EPI-MIPs.

A Semiflexible Polymer Translocation Through a Cylindrical Channel

In this study, translocation of a semi flexible polymer through a cylindrical channel have been investigated. A two-dimensional Monte Carlo simulation was employed, by utilizing the bond fluctuation method (BFM) to investigate the translocation processes of a chain length N. To surmount the entropic barrier, the middle monomers of the polymer have been positioned at the center of the pore, which is situated between the CIS and TRANS regions. Consequently, the static properties of a semi-flexible polymer by calculating the mean square end-to-end distance ‹R2› and the mean square radius of gyration ‹R<sup>g</sup>2› as functions of the chain length (N) have been examined. The mean square end-to-end distance and the mean square radius of gyration are proportional to the number of monomers N as ‹R2› ~ N1.496 and ‹R2g› ~ N1.505 correspondingly for a short cylindrical channel length L = 2, which aligns with the theoretically predicted. These finding indicates that the relationships between ‹R2› and ‹R<sup>g</sup>2› and the polymer chain size N are strongly influenced by the channel length L. The dynamic properties by analyzing the translocation time of the polymers also studied. Additionally, the relationship between the escape time τ and the polymer chain length N depends on the pore width W, which is equivalent to the diameter of the cylindrical channel. These research demonstrates that the escape time τ decreases as the width increases and escape time τ increases as the chain stiffness increases.