Comparative study of the interactions between C60 fullerene and SARS-CoV-2, HIV, eukaryotic, and bacterial model membranes: Insights into antimicrobial strategies with C60-peptide hybrids.

The neutrophil-derived peptide, indolicidin, and the sphere-shaped carbon nanoparticle, C60, are contemporary components capable of acting as bactericides and virucides, among others. Herein, the coarse-grained molecular dynamics simulation method was used to simulate the interactions of gram-negative bacteria, eukaryotes, human immunodeficiency virus (HIV), and SARS-COV-2 membrane models with indolicidin, C60s, and C60-indolicidin hybrids. Our results demonstrated that the carbon nanoparticle penetrated all membrane models, except the bacterial membrane, which remained impenetrable to both the peptide and C60. Additionally, the membrane thickness did not change significantly. The peptide floated above the membranes, with only the side chains of the tryptophan (Trp)-rich site slightly permeating the membranes. After achieving stable contact between the membrane models and nanoparticles, the infiltrated C60s interacted with the unsaturated tail of phospholipids. The density results showed that C60s stayed close to indolicidin and continued to interact with it even after penetration. Indolicidin, especially its Trp-rich site, exhibited more contact with the head and tail of neutral phospholipids compared to other phospholipids. Moreover, both particles interacted with different kinds of glycosphingolipids located in the eukaryote membrane. This investigation has the potential to advance our knowledge of novel approaches to combat antimicrobial resistance.

Binding of Phosphate Species to Ca2+ and Mg2+ in Aqueous Solution.

Phosphate derivatives and their interaction with metal cations are involved in many important biological phenomena, so an accurate characterization of the phosphate-metal interaction is necessary to properly understand the role of phosphate-metal contacts in mediating biological function. Herein, we improved the standard 12-6 Lennard-Jones (LJ) potential via the usage of the 12-6-4 LJ model, which incorporates ion-induced dipole interactions. Via parameter scanning, we fine-tuned the 12-6-4 LJ polarizability values to obtain accurate absolute binding free energies for the phosphate anions H2PO4-, HPO42-, PO43- coordinating with Ca2+ and Mg2+. First, we modified the phosphate 12-6-4 LJ parameters to reproduce the solvation free energies of the series of phosphate anions using the thermodynamic integration (TI) method. Then, using the potential mean force (PMF) method, the polarizability of the metal-phosphate interaction was obtained. We show that the free energy profiles of phosphate ions coordinated to Ca2+ and Mg2+ generally show similar trends at longer metal-phosphate distances, while the absolute binding energy values increased with deprotonation. The resulting parameters demonstrate the flexibility of the 12-6-4 LJ-type nonbonded model and its usefulness in accurately describing cation-anion interactions.

Thermodynamics of Metal-Acetate Interactions.

Metal ions play crucial roles in protein- and ligand-mediated interactions. They not only act as catalysts to facilitate biological processes but are also important as protein structural elements. Accurately predicting metal ion interactions in computational studies has always been a challenge, and various methods have been suggested to improve these interactions. One such method is the 12-6-4 Lennard-Jones (LJ)-type nonbonded model. Using this model, it has been possible to successfully reproduce the experimental properties of metal ions in aqueous solution. The model includes induced dipole interactions typically ignored in the standard 12-6 LJ nonbonded model. In this we expand the applicability of this model to metal ion-carboxylate interactions. Using 12-6-4 parameters that reproduce the solvation free energies of the metal ions leads to an overestimation of metal ion-acetate interactions, thus, prompting us to fine-tune the model to specifically handle the latter. We also show that the standard 12-6 LJ model significantly falls short in reproducing the experimental binding free energy between acetate and 11 metal ions (Ni(II), Mg(II), Cu(II), Zn(II), Co(II), Cu(I), Fe(II), Mn(II), Cd(II), Ca(II), and Ag(I)). In this study, we describe optimized C4 parameters for the 12-6-4 LJ nonbonded model to be used with three widely employed water models (Transferable Intermolecular Potential with 3 Points (TIP3P), Simple Point Charge Extended (SPC/E), and Optimal Point Charge (OPC) water models). These parameters can accurately match the experimental binding free energy between 11 metal ions and acetate. These parameters can be applied to the study of metalloproteins and transition metal ion channels and transporters, as acetate serves as a representative of the negatively charged amino acid side chains from aspartate and glutamate.

Getting zinc into and out of cells.

Ion channels are specialized proteins located on the plasma membrane and control the movement of ions across the membrane. Zn ion plays an indispensable role as a structural constituent of various proteins, moreover, it plays an important dynamic role in cell signaling. In this chapter, we discuss computational insights into zinc efflux and influx mechanism through YiiP (from Escherichia coli and Shewanella oneidensis) and BbZIP (Bordetella bronchiseptica) transporters, respectively. Gaining knowledge about the mechanism of zinc transport at the molecular level can aid in developing treatments for conditions such as diabetes and cancer by manipulating extracellular and intracellular levels of zinc ions.

Critical points for the design and application of RNA silencing constructs for plant virus resistance.

Control of plant virus diseases is a big challenge in agriculture as is resistance in plant lines to infection by viruses. Recent progress using advanced technologies has provided fast and durable alternatives. One of the most promising techniques against plant viruses that is cost-effective and environmentally safe is RNA silencing or RNA interference (RNAi), a technology that could be used alone or along with other control methods. To achieve the goals of fast and durable resistance, the expressed and target RNAs have been examined in many studies, with regard to the variability in silencing efficiency, which is regulated by various factors such as target sequences, target accessibility, RNA secondary structures, sequence variation in matching positions, and other intrinsic characteristics of various small RNAs. Developing a comprehensive and applicable toolbox for the prediction and construction of RNAi helps researchers to achieve the acceptable performance level of silencing elements. Although the attainment of complete prediction of RNAi robustness is not possible, as it also depends on the cellular genetic background and the nature of the target sequences, some important critical points have been discerned. Thus, the efficiency and robustness of RNA silencing against viruses can be improved by considering the various parameters of the target sequence and the construct design. In this review, we provide a comprehensive treatise regarding past, present and future prospective developments toward designing and applying RNAi constructs for resistance to plant viruses.

Analysis of medicinal and therapeutic potential of Withania somnifera derivatives against COVID-19.

Apart from chemical and allopathic drugs, several medicinal plants contain phytochemicals that are potentially useful to counter the COVID-19 pandemic. Withania somnifera (Ashwagandha), which has a good effect on some viral infections, can be considered as a candidate against the virus. In the present study, thirty-nine natural compounds of Ashwagandha were investigated in terms of their binding to the important drug targets to treat the COVID-19. Although the molecular docking calculations reveal the binding affinities of the compounds to Mpro, TMPRSS2, NSP15, PLpro, Spike RBD + ACE2, RdRp and NSP12 as targets in controlling the coronavirus enzymes, Withanoside II is expected to be the most effective compound due to the high affinity in binding with many of considered targets. Furthermore, the Withanoside III, IV, V, X, and XI have favorable binding affinities as ligands with respect to the MM/GBSA calculations. The molecular dynamics simulations MD explore a stable hydrogen bond network between ligands and the active sites residues. Also, the dynamic fluctuations of the binding site residues verify their tight binding to ligands. Moreover, the stability of ligand-protein complexes is approved by the RMSD ranges lower than 0.5 Å in equilibration zone for all mentioned complexes. The TMPRSS2-Withanolide Q and Mpro-Withanoside IV complexes are the most stable pairs using the MM/GBSA calculations and MD simulation.Communicated by Ramaswamy H. Sarma.

TMPRSS2 receptor in terms of human relative proteins and Mpro and NSP15 receptors on coronavirus itself target are the effective target for inhibitory effects of Withania somnifera compounds.The highest binding affinity is related for WithanolideD, WithanolideQ, WithanosideIV, WithanosideIII, WithanosideV, WithanosideII, and 2,3-Didehydrosomnifericin ligands on the Spike RBD + ACE2, TMPRSS2, Mpro, PLpro, RdRp, NSP15, and NSP12 receptors, respectively.Withanolide compounds on human related proteins targets and Withanoside structures on coronavirus itself receptors have the highest inhibitory potential.Withanoside II ligand is expected to be the most effective compound due to the high affinity to bind to many considered targets.The stability of ligand-protein complexes is approved by the RMSD ranges lower than 0.5 Å in equilibration zone for WithanolideQ-TMPRSS2 and WithanosideIV-Mpro complexes.

Inbreeding affected differently on observations distribution of a growth trait in Iranian Baluchi sheep.

OBJECTIVE: Initial consequence of inbreeding is inbreeding depression which impairs the performance of growth, production, health, fertility and survival traits in different animal breeds and populations. The effect of inbreeding on economically important traits should be accurately estimated. The effect of inbreeding depression on growth traits in sheep has been reported in many breeds. Based on this, the main objective of the present research was to evaluate the impact of inbreeding on some growth traits of Iranian Baluchi sheep breed using quantile regression model. METHODS: Pedigree and growth traits records of 13,633 Baluchi lambs born from year 1989 to 2016 were used in this research. The traits were birth weight, weaning weight, six-month weight, nine-month weight, and yearling weight. The contribution, inbreeding and co-ancestry software was used to calculate the pedigree statistics and inbreeding coefficients. To evaluate the impact of inbreeding on different quantiles of each growth trait, a series of quantile regression models were fitted using QUANTREG procedure of SAS software. Annual trend of inbreeding was also estimated fitting a simple linear regression of lamb's inbreeding coefficient on the birth year. RESULTS: Average inbreeding coefficient of the population was 1.63 percent. Annual increase rate of inbreeding of the flock was 0.11 percent (p<0.01). The results showed that the effect of inbreeding in different quantiles of growth traits is not similar. Also, inbreeding affected differently on growth traits, considering lambs' sex and type of birth. CONCLUSION: Quantile regression revealed that inbreeding did not have similar effect on different quantiles of growth traits in Iranian Baluchi lambs indicating that at a given age and inbreeding coefficient, lambs with different sex and birth type were not equally influenced by inbreeding.

Predictors of Success Rate in Different Initial Respiratory Supports in Very Low Birthweight Infants with Respiratory Distress.

BACKGROUND: Ideal respiratory support for very low birth weight infants (VLBW) can be selected based on demographic and clinical status at birth. METHODS: In this prospective cohort study, we included 163 VLBW neonates treated with either invasive or non-invasive respiratory support in their first 72 hours of life in the neonatal intensive care unit of Mahdiyeh hospital, Tehran, Iran. We used descriptive statistics to describe the data, and multiple logistic regression to determine the factors associated with the success rate of different strategies and the choice of strategy for primary respiratory support. All analyses were done using SPSS version 20 and STATA version 12 at a significance level of 0.05. RESULTS: The success rates of initial respiratory supports with nasal continuous positive airway pressure (NCPAP), noninvasive positive pressure ventilation (NIPPV), and INSURE (intubation surfactant extubation) were 63.20%, 42.10% and 61.90%, respectively. The results of multiple logistic regression analysis showed patent arterial duct (PDA) (yes vs. no: OR = 0.42) had a significant effect on initial respiratory support success (P<0.05). Also, gestational age (>28 vs. ≤28 weeks: OR = 0.26) and 5-min APGAR (≤6 vs. >6: OR = 9.69) had a significant effect on the choice of initial respiratory support in VLBW infants (P<0.05). CONCLUSION: The neonatal clinical condition may be a predictor of success for initial respiratory support at birth. Since the arterial duct may be open during the first hours of life, more study is needed to verify if early closure of the arterial duct may help increase the success rate of non-invasive respiratory support.

Molecular Basis for Membrane Selectivity of Antimicrobial Peptide Pleurocidin in the Presence of Different Eukaryotic and Prokaryotic Model Membranes.

Pleurocidin, a 25-residue cationic peptide, has antimicrobial activity against bacteria and fungi but exhibits very low hemolytic activity against human red blood cells (RBC). The peptide inserts into the bacterial membrane and causes the membrane to become permeable by either toroidal or carpet mechanism. Herein, to investigate the molecular basis for membrane selectivity of Pleurocidin, the interaction of the peptide with the different membrane models including the RBC, DOPC, DOPC/DOPG (3:1), POPE/POPG (3:1), and POPE/POPG (1:3) bilayers were studied by performing all-atom molecular dynamics (MD) simulation. The MD results indicated that the peptide interacted weakly with the neutral phospholipid bilayers (DOPC), whereas it made strong interactions with the negatively charged phospholipids. Pleurocidin maintained its α-helical structure during interactions with the anionic model membranes, but the peptide lost its secondary structure adjacent to the neutral model membranes. The results also revealed that the Trp-2, Phe-5, and Phe-6 residues, located in the N-terminal region of the peptide, played major roles in the insertion of the peptide into the model membranes. In addition, the peptide deeply inserted into the DOPC/DOPG membrane. The order analysis showed that Pleurocidin affected the order of anionic phospholipids more than zwitterionic phospholipids. The cholesterol molecules help the RBC membrane conserve integrity in response to Pleurocidin. This research has provided data on the Pleurocidin-membrane interactions and the reasons of resistance of eukaryotic membrane to the Pleurocidin at atomic details that are useful to develop potent AMPs targeting multidrug-resistant bacteria.

The role of intermolecular interactions on the encapsulation of human insulin into the chitosan and cholesterol-grafted chitosan polymers.

Chitosan and its derivatives used in drug delivery investigations could contribute to improving peptide and protein drug delivery systems. Herein, the molecular dynamics (MD) simulation approach was applied to evaluate the important driving factors of the human insulin encapsulation into the chitosan and cholesterol-modified chitosan polymers. The MD results revealed that the native conformation of insulin was stabilized by the chitosan polymers. In the present study, the effect of cholesterol moieties of modified chitosan was also examined and the results indicated that the cholesterol components would decrease the tendency of chitosan polymers to human insulin. Further analyses showed that the intermolecular interactions between the tyrosine, phenylalanine, and acidic residues are important in the formation of the insulin-polymer complexes. Another interesting finding was that the van der Waals, electrostatic, and CH-π interactions play key roles in the encapsulation process. Generally, in the case of human insulin, the MD simulation results would seem to suggest that the chitosan nanoparticles could be the more suitable carrier than the cholesterol-grafted chitosan nanoparticles.

Molecular Self-Assembly Strategy for Encapsulation of an Amphipathic α-Helical Antimicrobial Peptide into the Different Polymeric and Copolymeric Nanoparticles.

Encapsulation of peptide and protein-based drugs in polymeric nanoparticles is one of the fundamental fields in controlled-release drug delivery systems. The molecular mechanisms of absorption of peptides to the polymeric nanoparticles are still unknown, and there is no precise molecular data on the encapsulation process of peptide and protein-based drugs. Herein, the self-assembly of different polymers and block copolymers with combinations of the various molecular weight of blocks and the effects of resultant polymer and copolymer nanomicelles on the stability of magainin2, an α-helical antimicrobial peptide, were investigated by means of all-atom molecular dynamics (MD) simulation. The micelle forming, morphology of micellar aggregations and changes in the first hydration shell of the micelles during micelles formation were explored as well. The results showed that the peptide binds to the polymer and copolymer micelles and never detaches during the MD simulation time. In general, all polymers and copolymers simultaneously encapsulated the peptide during micelles formation and had the ability to maintain the helical structure of the peptide, whereas the first hydration shell of the peptide remained unchanged. Among the micelles, the polyethylene glycol (PEG) micelles completely encapsulated magainin2 and, surprisingly, the NMR structure of the peptide was perfectly kept during the encapsulation process. The MD results also indicated that the aromatic and basic residues of the peptide strongly interact with polymers/copolymers and play important roles in the encapsulation mechanism. This research will provide a good opportunity in the design of polymer surfaces for drug delivery applications such as controlled-release peptide delivery systems.

Direct Three-Dimensional Observation of Core/Shell-Structured Quantum Dots with a Composition-Competitive Gradient.

Synthesizing semiconductor nanoparticles through core/shell structuring is an effective strategy to promote the functional, physical, and kinetic performance of optoelectronic materials. However, elucidating the internal structure and related atomic distribution of core/shell structured quantum dots (QDs) in three dimensions, particularly at heterostructure interfaces, has been an overarching challenge. Herein, by applying complementary analytical techniques of electron microscopy and atom probe tomography, the dimensional, structural, topological, and compositional information on commercially available 11.8 nm-sized CdSSe/ZnS QDs were obtained. Systematic experiments at high resolution reveal the presence of a 1.8 nm-thick Cd xZn1 - xS inner shell with a composition gradient between the CdSe core and the ZnS outermost shell. More strikingly, the inner shell shows compositional variation because of competitive atomic configuration between Cd and ZnS, but it structurally retains a zinc-blende crystal structure with the core. The inner shell may grow through the decreased reactivity of S with Cd, followed by atomic diffusion-related processes. The composition-competitive gradient inner shell alleviates lattice misfit strain at heterostructure interfaces, thereby enhancing the quantum yield and photostabilty to a greater extent than those of other single-shell structures. Thus, this precise measurement approach could offer a potential pathway to develop a wide variety of three-dimensional core/shell-structured materials.

Molecular insights into the interactions of GF-17 with the gram-negative and gram-positive bacterial lipid bilayers.

The cationic antimicrobial peptide GF-17, a 17-mer-derived peptide from human cathelicidin LL-37, has a significant strength in the killing of the methicillin-resistant Staphylococcus aureus and Escherichia coli strains. Herein, we conducted a series of all-atom molecular dynamics simulations to investigate the ability of GF-17 in perturbing the model membranes of the gram-positive, S. aureus, and gram-negative, E. coli, bacteria. We also explored the contributions of the specific residues in the peptide activity. The molecular dynamics results indicated that the peptide is stabilized on the membrane surface and rapidly binds to the phosphate headgroups of the model membranes through the electrostatic interactions and hydrogen bonds. Furthermore, both polar and nonpolar interactions are energetically favored for the binding with the membrane surface. The research also revealed the important roles of the phenylalanine residues in the early insertion of the peptide into the bacterial model membranes. In addition, the results demonstrated that the central residues Arg23 and Lys25 played a critical role in the binding of GF-17 to both gram-negative and gram-positive model membranes, in excellent agreement with experimental studies. This study emphasizes on the pivotal role of basic residues in prompt association of the peptide on the model membrane surface and on the significance of residues Phe17, Ile24, Phe27, and Val32 in hydrophobic interactions. Therefore, our observations provide insights into the membrane-GF-17 interactions at atomic details that are useful to develop potent antimicrobial peptides targeting multidrug-resistant bacteria.

The potential impact of carboxylic-functionalized multi-walled carbon nanotubes on trypsin: A Comprehensive spectroscopic and molecular dynamics simulation study.

In this study, we report a detailed experimental, binding free energy calculation and molecular dynamics (MD) simulation investigation of the interactions of carboxylic-functionalized multi-walled carbon nanotubes (COOH-f-MWCNTs) with porcine trypsin (pTry). The enzyme exhibits decreased thermostability at 330K in the presence of COOH-f-MWCNTs. Furthermore, the activity of pTry also decreases in the presence of COOH-f-MWCNTs. The restricted diffusion of the substrate to the active site of the enzyme was observed in the experiment. The MD simulation analysis suggested that this could be because of the blocking of the S1 pocket of pTry, which plays a vital role in the substrate selectivity. The intrinsic fluorescence of pTry is quenched with increase in the COOH-f-MWCNTs concentration. Circular dichroism (CD) and UV-visible absorption spectroscopies indicate the ability of COOH-f-MWCNTs to experience conformational change in the native structure of the enzyme. The binding free energy calculations also show that electrostatics, π-cation, and π-π stacking interactions play important roles in the binding of the carboxylated CNTs with pTry. The MD simulation results demonstrated that the carboxylated CNTs adsorb to the enzyme stronger than the CNT without the-COOH groups. Our observations can provide an example of the nanoscale toxicity of COOH-f-MWCNTs for proteins, which is a critical issue for in vivo application of COOH-f-MWCNTs.

The Molecular Basis of the Sodium Dodecyl Sulfate Effect on Human Ubiquitin Structure: A Molecular Dynamics Simulation Study.

To investigate the molecular interactions of sodium dodecyl sulfate (SDS) with human ubiquitin and its unfolding mechanisms, a comparative study was conducted on the interactions of the protein in the presence and absence of SDS at different temperatures using six independent 500 ns atomistic molecular dynamics (MD) simulations. Moreover, the effects of partial atomic charges on SDS aggregation and micellar structures were investigated at high SDS concentrations. The results demonstrated that human ubiquitin retains its native-like structure in the presence of SDS and pure water at 300 K, while the conformation adopts an unfolded state at a high temperature. In addition, it was found that both SDS self-assembly and the conformation of the resulting protein may have a significant effect of reducing the partial atomic charges. The simulations at 370 K provided evidence that the SDS molecules disrupted the first hydration shell and expanded the hydrophobic core of ubiquitin, resulting in complete protein unfolding. According to these results, SDS and temperature are both required to induce a completely unfolded state under ambient conditions. We believe that these findings could be useful in protein folding/unfolding studies and structural biology.

Insight into the interactions, residue snorkeling, and membrane disordering potency of a single antimicrobial peptide into different lipid bilayers.

Pardaxin, with a bend-helix-bend-helix structure, is a membrane-active antimicrobial peptide that its membrane activity depends on the lipid bilayer composition. Herein, all-atom molecular dynamics (MD) simulations were performed to provide further molecular insight into the interactions, structural dynamics, orientation behavior, and cationic residues snorkeling of pardaxin in the DMPC, DPPC, POPC, POPG, POPG/POPE (3:1), and POPG/POPE (1:3) lipid bilayers. The results showed that the C-terminal helix of the peptide was maintained in all six types of the model-bilayers and pardaxin was tilted into the DMPC, DPPC, and POPG/POPE mixed bilayers more than the POPC and POPG bilayers. As well as, the structure of zwitterionic membranes was more affected by the peptide than the anionic bilayers. Taken together, the study demonstrated that the cationic residues of pardaxin snorkeled toward the interface of lipid bilayers and all phenylalanine residues of the peptide played important roles in the peptide-membrane interactions. We hope that this work will provide a better understanding of the interactions of antimicrobial peptides with the membranes.

Identification of the Crucial Residues in the Early Insertion of Pardaxin into Different Phospholipid Bilayers.

Antimicrobial peptides (AMPs) are part of the innate host defense system, and they are produced by living organisms to defend themselves against infections. Pardaxin is a cationic AMP with antimicrobial and antitumor activities that has potential to be used as a novel antibiotic or for drug delivery in cancer therapy. This peptide acts on the membrane of target cells and can lead to lysis using different mechanisms of action. Here, we conducted 4.5 µs all-atom molecular dynamics (MD) simulations to determine the critical fragments and residues of Pardaxin for early insertion into different lipid bilayers. Our results revealed that the N-terminal domain of the peptide, particularly the Phe 2 and (/or) Phe 3 residues, has a crucial role in early insertion, independent of the type of lipid bilayers.

Intralesional immunotherapy compared to cryotherapy in the treatment of warts.

BACKGROUND: Warts are the most common clinical manifestation of the human papilloma-virus infection in the skin and mucous membranes. In spite of the various therapeutic modalities for nongenital skin warts, there is still no single method to be used as an approved treatment. In this study, we compared the efficacy of immunotherapy and cryotherapy on wart lesions. METHODS: Sixty patients with verruca vulgaris and plantar warts were randomly divided into two groups. One group received intralesional injection of candida antigen repeated every 3 weeks until complete improvement of all warts or for a maximum of three sessions. The second group was treated by cryotherapy with liquid nitrogen for a maximum of ten sessions or until clearance of all lesions. T-test and chi-square test were used for statistical analysis, and P < 0.05 was considered statistically significant. RESULTS: The patients showed a significant therapeutic response to immunotherapy compared to cryotherapy (P = 0.023). Moreover, a significant difference was observed between the time-elapsed before treatment and the therapeutic response between both groups (P = 0.041). 76.7% of patients were completely cured with immunotherapy, while only 56.7% responded to cryotherapy. Complete remission was observed with fewer sessions (20.17 ± 0.65) in immunotherapy compared to cryotherapy (3.82 ± 2.481), but no statistically significant difference was shown between groups. Immunotherapy was well-tolerated except for the pain during injection that was the most common side effect. CONCLUSIONS: Intralesional immunotherapy is an effective treatment of warts. This method has a better therapeutic response, needs fewer sessions, and is capable of treating distant warts.

Molecular Insight into Human Lysozyme and Its Ability to Form Amyloid Fibrils in High Concentrations of Sodium Dodecyl Sulfate: A View from Molecular Dynamics Simulations.

Changes in the tertiary structure of proteins and the resultant fibrillary aggregation could result in fatal heredity diseases, such as lysozyme systemic amyloidosis. Human lysozyme is a globular protein with antimicrobial properties with tendencies to fibrillate and hence is known as a fibril-forming protein. Therefore, its behavior under different ambient conditions is of great importance. In this study, we conducted two 500000 ps molecular dynamics (MD) simulations of human lysozyme in sodium dodecyl sulfate (SDS) at two ambient temperatures. To achieve comparative results, we also performed two 500000 ps human lysozyme MD simulations in pure water as controls. The aim of this study was to provide further molecular insight into all interactions in the lysozyme-SDS complexes and to provide a perspective on the ability of human lysozyme to form amyloid fibrils in the presence of SDS surfactant molecules. SDS, which is an anionic detergent, contains a hydrophobic tail with 12 carbon atoms and a negatively charged head group. The SDS surfactant is known to be a stabilizer for helical structures above the critical micelle concentration (CMC) [1]. During the 500000 ps MD simulations, the helical structures were maintained by the SDS surfactant above its CMC at 300 K, while at 370 K, human lysozyme lost most of its helices and gained ß-sheets. Therefore, we suggest that future studies investigate the ß-amyloid formation of human lysozyme at SDS concentrations above the CMC and at high temperatures.

Restless legs syndrome in hemodialysis patients.

Restless legs syndrome (RLS) is a neurological disorder characterized by uncomfortable sensation of paresthesia in legs that subsequently causes involuntary and continuous movement of the lower limbs, especially at rest. Its prevalence in hemodialysis is more than that in the general population. Different risk factors have been suggested for RLS. We studied the prevalence and risk factors of RLS in 137 hemodialysis patients followed up at our center. The patients completed at least three months on dialysis and fulfilled four criteria for the diagnosis of RLS. We compared the patients with and without RLS, and the odds ratios (ORs) were estimated by the logistic regression models. The prevalence of RLS was 36.5% in the study patients. Among the variables, diabetes was the only predicting factor for the development of RLS. The diabetic patients may be afflicted with RLS 2.25 times more than the non-diabetics. Women developed severe RLS 5.23 times more than men. Neurodegeneration, decrease in dopamine level, higher total oxidant status, and neuropathy in diabetic patients may explain the RLS symptoms.