Radius Of Gyration Research Articles

Hydrogen-bond induced non-linear size dependence of lysozyme under the influence of aqueous glyceline.

Natural deep eutectic solvents (NADESs) are environmentally friendly green solvents and hold great promise in the pharmaceutical industry. The secondary structure of a protein, lysozyme, follows a non-monotonous behavior in aqueous glyceline (choline chloride + glycerol) as the wt. % of water is increased. However, it is unclear how the hydration affects the stability of the protein in a non-linear way. In this work, we have performed all-atom molecular dynamic simulations for 1 μs with the lysozyme protein in an aqueous glyceline deep eutectic solvent (DES) by varying the wt. % of water. The simulated radius of gyration, Rg, values can qualitatively reproduce the protein behavior such that the Rg increases initially with an increase in wt. % of water, reaches the peak at 40 wt. %, and then gradually decreases with dilution. Several other properties, including root mean square deviation, root-mean square fluctuation, secondary structure of the protein, and solvent accessible surface area, are examined to explore the NADES effect on the protein structure. Next, we analyze the hydrogen bond profile of intra-protein and among various interspecies, e.g., protein-DES, DES-DES, protein-water, and water-water. The variation in protein-protein hydrogen bonds with concentrations can qualitatively explain the non-linear conformational dependence of the protein. The radial distribution function analyses show various microscopic structures formed due to the DES and water interaction, which play a critical role in protein behavior. This study indicates that at lower wt. % of water, the protein is constrained in a strong hydrogen bond network formed by glycerol and water molecules, resulting in a lower Rg. As the wt. % of water increases, the protein-water interaction drives the protein to expand, reflecting an increasing Rg. At sufficiently higher wt. % of water, the DES constituent and the water molecules interact strongly with the protein, resulting in a decrease in Rg. Overall, the investigation offers a microscopic insight into the protein conformation in DES.

Sizes, conformational fluctuations, and SAXS profiles for intrinsically disordered proteins.

The preponderance of intrinsically disordered proteins (IDPs) in the eukaryotic proteome, and their ability to interact with each other, and with folded proteins, RNA, and DNA for functional purposes, have made it important to quantitatively characterize their biophysical properties. Toward this end, we developed the transferable self-organized polymer (SOP-IDP) model to calculate the properties of several IDPs. The values of the radius of gyration ( ) obtained from SOP-IDP simulations are in excellent agreement (correlation coefficient of 0.96) with those estimated from SAXS experiments. For AP180 and Epsin, the predicted values of the hydrodynamic radii ( ) are in nearly quantitative agreement with those from fluorescence correlation spectroscopy (FCS) experiments. Strikingly, the calculated SAXS profiles for 36 IDPs are also nearly superimposable on the experimental profiles. The dependence of and the mean end-to-end distance ( ) on chain length, , follows Flory's scaling law, ( and ), suggesting that globally IDPs behave as synthetic polymers in a good solvent. This finding depends on the solvent quality, which can be altered by changing variables such as pH and salt concentration. The values of and are 0.20 and 0.48 nm, respectively. Surprisingly, finite size corrections to scaling, expected on theoretical grounds, are negligible for and . In contrast, only by accounting for the finite sizes of the IDPs, the dependence of experimentally measurable on can be quantitatively explained using . Although Flory scaling law captures the estimates for , , and accurately, the spread of the simulated data around the theoretical curve is suggestive of of sequence-specific features that emerge through a fine-grained analysis of the conformational ensembles using hierarchical clustering. Typically, the ensemble of conformations partitions into three distinct clusters, having different equilibrium populations and structural properties. Without any further readjustments to the parameters of the SOP-IDP model, we also obtained nearly quantitative agreement with paramagnetic relaxation enhancement (PRE) measurements for α-synuclein. The transferable SOP-IDP model sets the stage for several applications, including the study of phase separation in IDPs and interactions with nucleic acids.

Understanding Anti-Polyelectrolyte Effect in Polyzwitterions Using Coarse-Grained Molecular Dynamics Simulations.

Polyzwitterions (PZs)─polymers bearing both positive and negative charges within each repeating unit─exhibit an unusual antipolyelectrolyte effect where their solubility and viscosity increase upon the addition of salt, contrary to typical polyelectrolytes. As model synthetic analogues of intrinsically disordered proteins, PZs in dilute aqueous solutions are expected to adopt either globular or random coil conformations, with salt addition influencing these structures. We employed coarse-grained Langevin dynamics simulations to investigate how structural parameters─specifically, the spacing between dipolar side chains (d), and the overall polymer chain length (N)─affect the conformational properties of polyzwitterions in salt solutions. Our simulations reveal that added salt leads to nonmonotonic changes in the polymer's radius of gyration, exhibiting both antipolyelectrolyte and polyelectrolyte effects depending on the salt concentration. This behavior is attributed to charge regulation and screening of dipole-dipole interactions by ions. Understanding and controlling the conformations of PZs in aqueous solutions by adjusting salt concentration is of paramount interest for applications in antimicrobial materials, antifouling coatings, drug delivery, membranes, and polymer electrolytes.

Accelerated Missense Mutation Identification in Intrinsically Disordered Proteins Using Deep Learning.

We use a combination of Brownian dynamics (BD) simulation results and deep learning (DL) strategies for the rapid identification of large structural changes caused by missense mutations in intrinsically disordered proteins (IDPs). We used ∼6500 IDP sequences from MobiDB database of length 20-300 to obtain gyration radii from BD simulation on a coarse-grained single-bead amino acid model (HPS2 model) used by us and others [Dignon, G. L. PLoS Comput. Biol. 2018, 14, e1005941,Tesei, G. Proc. Natl. Acad. Sci. U.S.A. 2021, 118, e2111696118,Seth, S. J. Chem. Phys. 2024, 160, 014902] to generate the training sets for the DL algorithm. Using the gyration radii ⟨Rg⟩ of the simulated IDPs as the training set, we develop a multilayer perceptron neural net (NN) architecture that predicts the gyration radii of 33 IDPs previously studied by using BD simulation with 97% accuracy from the sequence and the corresponding parameters from the HPS model. We now utilize this NN to predict gyration radii of every permutation of missense mutations in IDPs. Our approach successfully identifies mutation-prone regions that induce significant alterations in the radius of gyration when compared to the wild-type IDP sequence. We further validate the prediction by running BD simulations on the subset of identified mutants. The neural network yields a (104-106)-fold faster computation in the search space for potentially harmful mutations. Our findings have substantial implications for rapid identification and understanding of diseases related to missense mutations in IDPs and for the development of potential therapeutic interventions. The method can be extended to accurate predictions of other mutation effects in disordered proteins.

Thermally Conductive Naphthalene Epoxy Resin by Tailoring Flexible Chain Length and Liquid Crystal Structure

Epoxy resin with high thermal conductivity (λ) are widely used in electronic packaging, bonding, and coating. However, those with high intrinsic λ, typically synthesized using biphenyl or aromatic rings extended by ester linkages as the mesogenic unit, often exhibit high liquid crystal transition temperatures and poor processability. In this study, a series of naphthalene‐based liquid crystal epoxy monomers (LCE) were synthesized, using naphthalene as the mesogenic unit and modifying the flexible chain length on both sides. The resulting LCE were cured within their liquid crystal phase to form naphthalene liquid crystal epoxy resin (LCER). The results show that the network order, radius of gyration, and low‐frequency vibrational density of states all initially increase and then decrease with increasing flexible chain length. For LCER2, with a three‐carbon flexible chain, these parameters reach their maximum values, facilitating phonon diffusion and enhancing λ. The liquid crystal transition temperature, λ, heat resistance index, and storage modulus of LCER2 were 67~78oC, 0.40 W/(m·K), 158.8oC and 2059 MPa, respectively, approximately 2.2 times higher than that of E‐51 resin (0.18 W/(m·K)). This work offers insights into designing epoxy resins with low liquid crystal transition temperature, high intrinsic λ, and excellent mechanical properties for thermal management.

Preparation of Temperature Resistant Terpolymer Fracturing Fluid Thickener and Its Working Mechanism Study via Simulation Methods.

To enhance oil and gas recovery, a novel hydrophobic terpolymer was synthesized via free radical polymerization. The terpolymer consists of acrylamide, acrylic acid, and hydrophobic monomers, and is used as a hydraulic fracturing fluid thickener for freshwater environments. Hydrophobic groups were introduced into terpolymer to improve its tackiness and temperature resistance. The conformation and key parameters of hydrophobic monomers at different temperatures were investigated through a combination of experiments and molecular dynamics simulations. These methods were employed to elucidate the mechanism behind its high-temperature resistance. The experiment results show that, at concentrations between 0.2% and 0.4%, significant intermolecular aggregation occurs, leading to a substantial increase in solution viscosity. Configuring the base fluid of synthetic polymer fracturing fluid with 1% doping, the apparent viscosities of the base fluid were 129.23 mPa·s and 133.11 mPa·s, respectively. The viscosity increase rate was 97%. The base fluid was crosslinked with 1.5% organozirconium crosslinker to form a gel. The controlled loss coefficient and loss velocity of the filter cake were C3 = 0.84 × 10-3 m/min1/2 and vc = 1.40 × 10-4 m/min at 90 °C, meeting the technical requirements for water-based fracturing fluid. Molecular dynamics simulations revealed that the radius of gyration of the hydrophobically linked polymer chain segments decreases as the temperature increases. This is due to the increased thermal motion of the polymer chain segments, resulting in less stretching and intertwining of the chains. As a result, the polymer chains move more freely, which decreases the viscosity of the solution. In conclusion, the proposed fracturing fluid thickener system demonstrates excellent overall performance and shows significant potential for application in oil and gas recovery.

Identification of potential plant secondary metabolites targeting begomovirus-associated betasatellite virulence factor βC1 protein through molecular docking, simulation and MM-PBSA studies

The βC1 protein encoded by begomoviruses plays a key role in counteracting plant defense mechanisms, making it a prime target for antiviral compounds. Here, we investigated the role of plant secondary metabolites for their antiviral potential. Initially, the tertiary structure of βC1 protein was predicted and docked to 2851 plant secondary metabolites along with positive controls ribavirin and ningnanmycin. Additionally, 43 analogues of the ligand with highest dock score were created and assessed against the βC1 protein to see if they offered better binding energy than the initial compound. To check the protein–ligand complex's stability, we performed a 100 ns molecular dynamics (MD) simulation, then measured the change in Gibbs free energy (ΔG) using the molecular mechanics/Poisson-Boltzmann surface area (MM-PBSA) approach. Our study found that Anonaine, a bioactive compound, had a high binding score of − 6.0 kcal/mol, with its analogues a33 and a41 scoring − 6.8 kcal/mol and − 6.6 kcal/mol, respectively. Molecular dynamics simulations for these complexes showed stable interactions, with minimal changes in root mean square deviation (RMSD) and root mean square fluctuation (RMSF) values. Additionally, the protein–ligand complexes showed consistent hydrogen bond formation, with negligible changes in the radius of gyration (Rg) and solvent-accessible surface area (SASA). The binding free energy (ΔG) calculations revealed estimated values of − 16.99 ± 2.16, − 18.29 ± 1.91, and − 27.26 ± 2.11 for the βC1-Anonaine, βC1-a33, and βC1-a44 protein–ligand complexes, respectively. In silico toxicity predictions suggest top ligands are less toxic, making them ideal for biopesticide development. Overall, these findings reveal the potential of plant secondary metabolites as promising agents in controlling begomovirus infections.Graphical

Structural Implications of HIV-1 Protease Subtype C Bound to Darunavir: A Molecular Dynamics Study.

In recent years, Human Immunodeficiency Virus (HIV) remains a significant global health challenge, with millions affected worldwide, particularly in Africa and sub-Saharan regions. Despite advances in antiretroviral therapies, the genetic variability of HIV, including different subtypes and drug-resistant strains, poses persistent obstacles in the development of universally effective treatments. This study focuses on the dynamics of HIV protease, a key enzyme in viral replication and maturation, particularly targeting subtype C and its double insertion (HL) variant L38HL, in the context of interaction with Darunavir (DRV), a second-generation nonpeptidic protease inhibitor approved by the FDA in 2006. Through molecular dynamics simulations, structural analyses, dynamic cross-correlation analyses, and binding energy calculations, we investigated differences in the binding of DRV to WT and L38HL HIV-1 protease. The findings highlight that the double insertion at the hinge induces variation in Φ and Ψ angles, leading to increased residue fluctuations, solvent-accessible surface area (SASA), and radius of gyration (Rg). This alters the overall structural compactness and the hydrophobic core crucial for drug binding. Subtle structural changes result in the loss of hydrogen bond interactions, reducing the binding energy of L38HL HIV-1 protease subtype C bound to DRV, leading to drug resistance.

A conformational fingerprint for amyloidogenic light chains.

Both immunoglobulin light-chain (LC) amyloidosis (AL) and multiple myeloma (MM) share the overproduction of a clonal LC. However, while LCs in MM remain soluble in circulation, AL LCs misfold into toxic-soluble species and amyloid fibrils that accumulate in organs, leading to distinct clinical manifestations. The significant sequence variability of LCs has hindered the understanding of the mechanisms driving LC aggregation. Nevertheless, emerging biochemical properties, including dimer stability, conformational dynamics, and proteolysis susceptibility, distinguish AL LCs from those in MM under native conditions. This study aimed to identify a2 conformational fingerprint distinguishing AL from MM LCs. Using small-angle X-ray scattering (SAXS) under native conditions, we analyzed four AL and two MM LCs. We observed that AL LCs exhibited a slightly larger radius of gyration and greater deviations from X-ray crystallography-determined or predicted structures, reflecting enhanced conformational dynamics. SAXS data, integrated with molecular dynamics simulations, revealed a conformational ensemble where LCs adopt multiple states, with variable and constant domains either bent or straight. AL LCs displayed a distinct, low-populated, straight conformation (termed H state), which maximized solvent accessibility at the interface between constant and variable domains. Hydrogen-deuterium exchange mass spectrometry experimentally validated this H state. These findings reconcile diverse experimental observations and provide a precise structural target for future drug design efforts.

A conformational fingerprint for amyloidogenic light chains

Both immunoglobulin light-chain (LC) amyloidosis (AL) and multiple myeloma (MM) share the overproduction of a clonal LC. However, while LCs in MM remain soluble in circulation, AL LCs misfold into toxic-soluble species and amyloid fibrils that accumulate in organs, leading to distinct clinical manifestations. The significant sequence variability of LCs has hindered the understanding of the mechanisms driving LC aggregation. Nevertheless, emerging biochemical properties, including dimer stability, conformational dynamics, and proteolysis susceptibility, distinguish AL LCs from those in MM under native conditions. This study aimed to identify a2 conformational fingerprint distinguishing AL from MM LCs. Using small-angle X-ray scattering (SAXS) under native conditions, we analyzed four AL and two MM LCs. We observed that AL LCs exhibited a slightly larger radius of gyration and greater deviations from X-ray crystallography-determined or predicted structures, reflecting enhanced conformational dynamics. SAXS data, integrated with molecular dynamics simulations, revealed a conformational ensemble where LCs adopt multiple states, with variable and constant domains either bent or straight. AL LCs displayed a distinct, low-populated, straight conformation (termed H state), which maximized solvent accessibility at the interface between constant and variable domains. Hydrogen-deuterium exchange mass spectrometry experimentally validated this H state. These findings reconcile diverse experimental observations and provide a precise structural target for future drug design efforts.

Improving the antimicrobial activity of RP9 peptide through theoretical and experimental investigation.

Improving the antimicrobial activity of RP9 peptide through theoretical and experimental investigation.

Molecular simulations guiding recombinant mussel protein with enhanced applicable properties for adhesive materials.

Molecular simulations guiding recombinant mussel protein with enhanced applicable properties for adhesive materials.

Physicochemical characteristics of chitosan molecules: Modeling and experiments.

Physicochemical characteristics of chitosan molecules: Modeling and experiments.

Glycosylated peptides isolated from cheese whey have antifreezing activity.

Glycosylated peptides isolated from cheese whey have antifreezing activity.

Effects of modified KGM on the gelling capability of fish protein: Novel insights into hooking effect

Effects of modified KGM on the gelling capability of fish protein: Novel insights into hooking effect

Cancer-associated mutation at glycine 400 in TIP60 disrupt its phase separation property and catalytic activity resulting in compromised DNA damage repair function of the cell.

Cancer-associated mutation at glycine 400 in TIP60 disrupt its phase separation property and catalytic activity resulting in compromised DNA damage repair function of the cell.

Binding Affinity Prediction and Pesticide Screening against Phytophthora sojae Using a Heterogeneous Interaction Graph Attention Network-Based Model.

Phytophthora root and stem rot in soybeans results in substantial economic losses worldwide. In this study, a machine learning model based on a heterogeneous interaction graph attention network model was constructed. The PDBbind data set, comprising 13,285 complexes with experimental pKa or pKi values, was utilized to train and evaluate the model, which was subsequently employed to screen candidate compounds against chitin synthase of Phytophthora sojae (PsChs1) in the Traditional Chinese Medicine Systems Pharmacology database, comprising 14,249 compounds. High-scoring candidate compounds were docked with PsChs1 protein using Discovery Studio, and their interaction energies were evaluated. Molecular dynamic simulations spanning 50 ns were performed using GROMACS to explore the stability of the complexes, trajectory analysis was conducted with root-mean-square deviations, and the hydrogen bonds, radius of gyration, MMPBSA binding free energy, and binding modes were analyzed. MOL011832 and MOL011833 were identified as potential pesticides, both of which were present in the herb Schizonepeta through database retrieval. The inhibitory effects of an ethanol extract of Schizonepeta against P. sojae were subsequently explored and confirmed in biological experiments. Overall, this study proves the feasibility and high efficiency of pesticide discovery using graph neural network-based models.

Hydrogen bonds vs RMSD: Geometric reaction coordinates for protein folding.

Reaction coordinates are a useful tool that allows the complex dynamics of a protein in high-dimensional phase space to be projected onto a much simpler model with only a few degrees of freedom, while preserving the essential aspects of that dynamics. In this way, reaction coordinates could provide an intuitive, albeit simplified, understanding of the complex dynamics of proteins. Together with molecular dynamics (MD) simulations, reaction coordinates can also be used to sample the phase space very efficiently and to calculate transition rates and paths between different metastable states. Unfortunately, ideal reaction coordinates for a system capable of these performances are not known a priori, and an efficient calculation in the course of an MD simulation is currently an active field of research. An alternative is to use geometric reaction coordinates, which, although generally unable to provide quantitative accuracy, are useful for simplified mechanistic models of protein dynamics and can thus help gain insights into the fundamental aspects of these dynamics. In this study, five such geometric reaction coordinates, such as the end-to-end distance, the radius of gyration, the solvent accessible surface area, the root-mean-square distance (RMSD), and the mean native hydrogen bond length, are compared. For this purpose, extensive molecular dynamics simulations were carried out for two peptides and a small protein in order to calculate and compare free energy profiles with the aid of the reaction coordinates mentioned. While none of the investigated geometrical reaction coordinates could be demonstrated to be an optimal reaction coordinate, the RMSD and the mean native hydrogen bond length appeared to perform more effectively than the other three reaction coordinates.

The adsorption behavior at the air/water interface of saturated cardanol nonionic surfactants through molecular dynamic simulations.

Cardanol surfactants exhibit significant development potential owing to their advantages of abundant availability, low cost, and environmental sustainability. In this study, a series of saturated cardanol nonionic surfactants were designed. The structure-activity relationships of these surfactants with varying lengths and positions of PO and EO chains were investigated from three perspectives: surface activity, adsorption morphology, and molecular bonding forces. The results indicated that the chain length ratio and position of PO and EO significantly influenced the performance of cardanol nonionic surfactants at the air/water interface. The PO chains can significantly mitigate the solvation effect at the terminus of surfactants, thereby enhancing their aggregation at the air/water interface. Additionally, the ratio of PO to EO chains influences both the radius of gyration and tilt angle of hydrophilic and hydrophobic segments within surfactant molecules. Notably, when both PO and EO chain lengths are set to 8, optimal adsorption of surfactant molecules occurs at the interface. This phenomenon is primarily attributed to hydrogen bonding interactions that lead water molecules to exhibit varying degrees of aggregation around PO or EO chains; these effects, in conjunction with adsorption morphology, ultimately influence the interfacial properties of surfactants. This study provides a theoretical foundation and reference for the structural design, synthesis, and interfacial properties of cardanol surfactants. In this study, Packmol was employed for model construction, Gromacs for molecular dynamics simulations, and all simulations were conducted using the GAFF force field. The simulation process primarily involved the steepest descent method, followed by NPT ensemble simulations for 1ns and 10ns, respectively. The Berendsen and Parrinello-Rahman methods are employed to maintain system pressure. The LINCS algorithm and Lennard-Jones potential are utilized to effectively constrain molecular bond lengths and cutoff radius. The long-range electrostatic interactions are treated using the Particle-Mesh Ewald (PME) summation method.

The stability and self-assembly of tri-calcium silicate and hydroxyapatite scaffolds in bone tissue engineering applications

The fabrication of scaffolds for bone tissue engineering (BTE) applications often involves the utilization of two distinct categories of biomaterials, namely calcium phosphates and calcium silicates. The selection of these materials is based on their biocompatibility, bioactivity, and mechanical characteristics that closely resemble those of natural bone. The present research examined the utilization of hydroxyapatite (HAP) and tri-calcium silicate (TCS), which are among the most commonly utilized materials in calcium phosphates and calcium silicates, in the context of bone scaffolding applications. A molecular dynamics simulation was conducted to investigate the impact of different concentrations of ceramic nanoparticles, when combined with sodium alginate (SA) hydrogel, on the fabrication of bone scaffolds.The stability and self-assembly were assessed through several parameters, such as the solvent-accessible surface area (SASA), radius of gyration (Rg), radial distribution function (g(r)), root-mean-square deviation (RMSD), root-mean-square fluctuation (RMSF), hydrogen bonding, van der Waals, electrostatic, and total energies. The findings indicate that the addition of 10 wt% HAP and TCS to the SA hydrogel matrix results in a more compact, stable, and potentially less hydrated structure. Accordingly, the experimental validation of these simulation approved our in silico findings. Experimental rheology and mechanical properties evaluation validate our simulation results, indicating a superior characteristic of TCS10 and HAP10 inks and 3D-printed scaffolds among other composition ratios. This could potentially benefit the in vitro and in vivo performance of the scaffold and its interaction with cells. The aforementioned traits are considered fundamental for the successful execution of the scaffold in the field of BTE. The findings indicate that TCS samples exhibit superior properties when compared to HAP samples, specifically in terms of composition with SA hydrogel.