SARS-CoV-2 seroprevalence in the city of Hyderabad, India in early 2021.

Background: COVID-19 emerged as a global pandemic in 2020, spreading rapidly to most parts of the world. The proportion of infected individuals in a population can be reliably estimated via serosurveillance, making it a valuable tool for planning control measures. Our serosurvey study aimed to investigate SARS-CoV-2 seroprevalence in the urban population of Hyderabad at the end of the first wave of infections. Methods: This cross-sectional survey, conducted in January 2021 and including males and females aged 10 years and above, used multi-stage random sampling. 9363 samples were collected from 30 wards distributed over six zones of Hyderabad, and tested for antibodies against SARS-CoV-2 nucleocapsid antigen. Results: Overall seropositivity was 54.2%, ranging from 50% to 60% in most wards. Highest exposure appeared to be among those aged 30-39 and 50-59 years, with women showing greater seropositivity. Seropositivity increased with family size, with only marginal differences among people with varying levels of education. Seroprevalence was significantly lower among smokers. Only 11% of the survey subjects reported any COVID-19 symptoms, while 17% had appeared for COVID-19 testing. Conclusion: Over half the city's population was infected within a year of onset of the pandemic. However, ∼ 46% of people remained susceptible, contributing to subsequent waves of infection.

Force-Field Induced Bias in the Structure of Aß21-30: A Comparison of OPLS, AMBER, CHARMM, and GROMOS Force Fields.

In this work we examine the dynamics of an intrinsically disordered protein fragment of the amyloid ß, the Aß21-30, under seven commonly used molecular dynamics force fields (OPLS-AA, CHARMM27-CMAP, AMBER99, AMBER99SB, AMBER99SB-ILDN, AMBER03, and GROMOS53A6), and three water models (TIP3P, TIP4P, and SPC/E). We find that the tested force fields and water models have little effect on the measures of radii of gyration and solvent accessible surface area (SASA); however, secondary structure measures and intrapeptide hydrogen-bonding are significantly modified, with AMBER (99, 99SB, 99SB-ILDN, and 03) and CHARMM22/27 force-fields readily increasing helical content and the variety of intrapeptide hydrogen bonds. On the basis of a comparison between the population of helical and ß structures found in experiments, our data suggest that force fields that suppress the formation of helical structure might be a better choice to model the Aß21-30 peptide.

The stability of a ß-hairpin is altered by surface-water interactions under confinement.

Understanding protein folding and stability in in vivo confined environments is a challenging problem from both experimental and computational points of views. Despite recent insights, an appreciation and complete understanding of how the solvent influences the structure and stability of proteins under complex confined environments is still lacking. Here, using all-atom molecular dynamics simulations in explicit solvent, we report the effects of confinement on the lifetime of a metastable ß-hairpin structure in the Aß(21-30) decapeptide. Our results show that the values of these lifetimes depend on the nature of the confining surface, where smooth and rough hydrophobic confining walls have solvent-mediated stabilizing and destabilizing effects, respectively. The source of the destabilization found inside atomically rough confining walls lies in surface-peptide interactions that break the ß-hairpin in this peptide, whereas smooth confining walls stabilize it by forming well-ordered layers of water that keep the decapeptide solvated in the inner part of the pore and away from the surface. In addition, we show that the size of the confining pore can tune the value of the lifetimes where pore sizes comparable to the size of the decapeptide have the largest effects.

Effects of confinement on the structure and dynamics of an intrinsically disordered peptide: a molecular-dynamics study.

In vivo, proteins and peptides are exposed to radically different environments than those in bulk. Because of the abundance of other cellular components, proteins perform their function in crowded and confined spaces. Confinement has been shown to alter the structure, dynamics, and folding of proteins that possess a native fold. Little is known, however, of the effects of confinement on biologically important intrinsically disordered proteins or peptides (IDP). Here, we use extensive molecular dynamics simulations to investigate the effects of confinement in an IDP, the Aß21-30, a central folding nucleus of the full length amyloid ß-protein. In this study, we report results derived from 107 µs of molecular dynamics simulations that subjected the Aß21-30 to two types of confinement: hydrophilic and hydrophobic pores. Results show that turn structures are enhanced as a function of decreasing pore size (increasing confinement) over other structures, including coils, ß-hairpins, and bridges. However, the percentage occurrence of the dominant hydrogen bond between amino acids Asp23 and Ser26 shown to stabilize the turn in bulk simulations does not increase as a function of confinement signifying a disconnect between structure and internal hydrogen bonding. Differences in structure and dynamics of the decapeptide due to hydrophilic and hydrophobic confinement are more apparent at the extreme confinement conditions, where a reduction of the available phase space in hydrophilic confinement is explained in terms of interactions between the decapeptide and a layer of water at the interface between the decapeptide and the surface of the pore, and a smaller size of the decapeptide in the hydrophobic pores is rationalized in terms of peptide-surface interactions.

Dynamics of metastable ß-hairpin structures in the folding nucleus of amyloid ß-protein.

The amyloid ß-protein (Aß), which is present predominately as a 40- or 42-residue peptide, is postulated to play a seminal role in the pathogenesis of Alzheimer's disease (AD). Folding of the Aß(21-30) decapeptide region is a critical step in the aggregation of Aß. We report results of constant temperature all-atom molecular dynamics simulations in explicit water of the dynamics of monomeric Aß(21-30) and its Dutch [Glu22Gln], Arctic [Glu22Gly], and Iowa [Asp23Asn] isoforms that are associated with familial forms of cerebral amyloid angiopathy and AD. The simulations revealed a variety of loop conformers that exhibited a hydrogen bond network involving the Asp23 and Ser26 amino acids. A population of conformers, not part of the loop population, was found to form metastable ß-hairpin structures with the highest probability in the Iowa mutant. At least three ß-hairpin structures were found that differed in their hydrogen bonding register, average number of backbone hydrogen bonds, and lifetimes. Analysis revealed that the Dutch mutant had the longest ß-hairpin lifetime (≥500 ns), closely followed by the Iowa mutant (≈500 ns). Aß(21-30) and the Arctic mutant had significantly lower lifetimes (≈200 ns). Hydrophobic packing of side chains was responsible for enhanced ß-hairpin lifetimes in the Dutch and Iowa mutants, whereas lifetimes in Aß(21-30) and its Arctic mutant were influenced by the backbone hydrogen bonding. The data suggest that prolonged ß-hairpin lifetimes may impact peptide pathogenicity in vivo.

Maternal manganese restriction increases susceptibility to high-fat diet-induced dyslipidemia and altered adipose function in WNIN male rat offspring.

Growth in utero is largely a reflection of nutrient and oxygen supply to the foetus. We studied the effects of Mn restriction per se, maternal Mn restriction, and postnatal high-fat feeding in modulating body composition, lipid metabolism and adipocyte function in Wistar/NIN (WNIN) rat offspring. Female weanling, WNIN rats received ad libitum for 4 months, a control or Mn-restricted diet and were mated with control males. Some restricted mothers were rehabilitated with control diet from conception (MnRC) or parturition (MnRP), and their offspring were raised on control diet. Some restricted offspring were weaned onto control diet (MnRW), while others continued on restricted diet throughout (MnR). A set of offspring from each group was fed high-fat diet from 9 months onwards. Body composition, adipocytes function, and lipid metabolism were monitored in male rat offspring at regular intervals. Maternal manganese restriction increased the susceptibility of the offspring to high-fat-induced adiposity, dyslipidaemia, and a proinflammatory state but did not affect their glycemic or insulin status.

Effect of solvation on ion binding to imidazole and methylimidazole.

Quantum chemical [MP2(FULL)/6-311++G-(d,p)] calculations are done on the binding of hydrated Li(+), Na(+), K(+), Mg(2+), Cu(+), and Zn(2+) metal ions with biologically relevant heteroaromatics such as imidazole and methylimidazole. The computed interaction energies are found to be in good agreement with the available experimental data. The effect of hydration on hydrogen bonding has been studied in detail and it shows that the hydrogen bond strength between H(2)O···H-N(1) substantially increases in the presence of metal ions. The present study quantifies the cooperativity between M···imidazole (M = Li(+), Na(+), K(+), Mg(2+), Cu(+), and Zn(2+)) and N(1)-H···OH(2) interactions. Topological atoms in molecules (AIM) analysis and charge analysis support the variation in hydrogen-bonding strength and the variation in M···imidazole binding strength. Effect of hydration on N(1)-H stretching frequency is studied, and it shows a clear shift in the stretching frequency after sequential hydration of metal ion as well as the N(1) of imidazole. The present study provides a detailed account on the biologically important M-histidine motif interaction with metal ions, where histidine is modeled by imidazole and methylimidazole.

Explicit solvent effect on cation-pi interactions: a first principle investigation.

Sequential attachment of water molecules to cation-pi (Li+-benzene, K+-benzene, and Mg2+-benzene) systems reveals that the cation-pi interaction strength varies in opposite direction depending on the site of solvation of the cation-pi system. Solvation of the metal ion decreases its interaction energy with the pi system, while the solvation of the pi system increases its interaction energy with the metal ion. The cation binding to benzene clearly enhances the ability of aromatic protons to participate in hydrogen bonding with water molecules. The distance between the metal ion and centroid of the benzene inherently varies with the position of water molecules in the vicinity of cation-pi complex. Reduced variational space (RVS) analysis on bare and solvated cation-pi complexes indicates that the major contributions to the total interaction energy are coming from the polarization and charge transfer energy terms of the pi system. Topological atoms in molecules (AIM) analysis is performed to evaluate the nature of the cation-pi interaction. Good correlations are observed between interaction energies and charge density at the cage critical point of the cation-pi complexes.

Structural and energetic preferences of pi, sigma, and bidentate cation binding (Li(+), Na(+), and Mg(2+)) to aromatic amines (Ph-(CH(2))(n)-NH(2), n = 2-5): a theoretical study.

MP2/aug-cc-pVTZ calculations have been carried out to systematically explore three distinct binding preferences, namely, monodentate binding in pi and sigma fashions to aromatic and amine groups, respectively, and the bidentate mode of Li(+), Na(+) and Mg(2+) ions with aromatic amines (Ph-(CH(2))(n)-NH(2), n = 2-5). Several model systems were devised to examine the binding strength of the interactions where the aromatic and amine motifs are not interconnected. The sensitivity of structures and energetics to the basis set superposition error (BSSE) was examined by doing the geometry optimization with a counterpoise option at the MP2/6-31G(d) and MP2/cc-pVDZ levels. Variations in the binding affinities of Li(+), Na(+), and Mg(2+) metals to pi systems and -NH(2) groups are observed. The effects of the spacer chain orientation and its length on the binding of metal ions and protons to aromatic amines are studied. It is observed that Mg(2+) binding is sensitive to the spacer chain orientation and its length, whereas Li(+) or Na(+) binding is independent of spacer chain orientation and length. Reorganization energies are estimated for the complexation of metal ions to aromatic amines. It is observed that the reorganization energy for the complexation of Mg(2+) is slightly higher than that of Li(+), Na(+), and H(+).

Comprehensive study on the solvation of mono- and divalent metal cations: Li+, Na+, K+, Be2+, Mg2+ and Ca2+.

Hydration of mono- and divalent metal ions (Li(+), Na(+), K(+), Be(2+), Mg(2+) and Ca(2+)) has been studied using the DFT (B3LYP), second-order Møller-Plesset (MP2) and CCSD(T) perturbation theory as well as the G3 quantum chemical methods. Double-zeta and triple-zeta basis sets containing both (multiple) polarization and diffuse functions were applied. Total and sequential binding energies are evaluated for all metal-water clusters containing 1-6 water molecules. Total binding energies predicted at lower levels of theory are compared with those from the high level G3 calculations, whereas the sequential binding energies are compared with available experimental values. An increase in the quality of the basis set from double-zeta to triple-zeta has a significant effect on the sequential binding energies, irrespective of the geometries used. Within the same group (I or II), the sequential binding energy predictions at the MP2 and B3LYP vary appreciably. We noticed that, for each addition of a water molecule, the change of the M-O distance in metal-water clusters is higher at the B3LYP than at the MP2 level. The charge of the metal ion decreases monotonically as the number of water molecules increase in the complex.

The effect of spacer chain length on ion binding to bidentate alpha,omega-diamines: contrasting ordering for H+ and Li+ ion affinities.

Electrospray ionisation mass spectrometry studies and quantum chemical calculations indicate that bidentate ligation of Li+ ion to the diamines leads to symmetric bridging and exhibits contrasting relative affinity orderings compared to that of proton for alpha,omega-diamines.