Parameters of monovalent ions in the AMBER-99 forcefield: assessment of inaccuracies and proposed improvements

The monovalent ion parameters used by the AMBER-99 forcefield are shown to exhibit physically inaccurate behavior in molecular dynamics simulations of strong 1:1 electrolytes. These errors arise from an ad hoc adaptation of Aqvist's cation parameters. The result is the rapid formation of large, unphysical clusters at concentrations that are well below solubility limits. The observed unphysical behavior poses a serious challenge for simulating ions around highly charged polymers such as nucleic acids. In this communication, we explain the source of this unphysical behavior. To facilitate the continued use of the popular AMBER parameters, we prescribe a simple fix whereby Aqvist's cations and anions are used in conjunction with the AMBER forcefield for nucleic acids. A preliminary test of this strategy suggests that the proposed fix is reasonable and is likely to be generalizable for simulating diffuse and specific ion binding to nucleic acids.     

Carboranyl thymidine analogues for neutron capture therapy

Neutron capture therapy (NCT) is a binary radio-chemotherapeutic modality for the treatment of cancer. A major focus of NCT-related research is the development of novel tumor-selective agents that serve as the chemical component in NCT. Thymidine analogues substituted with a boron-containing carborane cluster at the N3 position, designated 3CTAs (3-carboranyl thymidine analogues), constitute one class of these new improved NCT agents. Their chemical, structural and biological properties are discussed in this Feature Article.     

Convective stability analysis of a micropolar fluid layer by variational method

This paper studies Rayleigh-Bénard convection of micropolar fluid layer heated from below with realistic boundary conditions. A specific approach for stability analysis of a convective problem based on variational principle is applied to characterize the Rayleigh number for quite general nature of bounding surfaces. The analysis consists of replacing the set of field equations by a variational principle and the expressions for Rayleigh number are then obtained by using trial function satisfying the essential boundary conditions. Further, the values of the Rayleigh number for particular cases of large and small values of the microrotation coefficient have been obtained. The effects of wave number and micropolar parameter on the Rayleigh numbers for onset of stationary instability for each possible combination of the bounding surfaces are discussed and illustrated graphically. The present analysis establishes that the nature of bounding surfaces combination and microrotation have significant effect on the onset of convection.     

Preliminary estimate of branching ratios of weak hadronic decays of bottom baryons emitting charmless scalar mesons

In this paper we study one-dimensional static self-dual non-topological solitons in an Abelian-Higgs Chern–Simons model with a non-canonical kinetic term. We choose a scalar potential with a single minimum and present an analytical soliton solution which corresponds to an electrically charged lump-like soliton without total momentum and located in a region where the scalar field gets maximum. The solitonic boundary conditions impose a discontinuity on the electric field across the soliton line where, then, there is a linear charge density.     

Evaluation of Glycosyl Hydrolases in the Secretome of <Emphasis Type="Italic">Aspergillus fumigatus</Emphasis> and Saccharification of Alkali-Treated Rice Straw

A thermotolerant Aspergillus fumigatus strain isolated from composting pile of mixed industrial waste was found to produce a spectrum of cellulase and hemicellulases when cultured on rice straw solidified substrate. The two-dimensional electrophoresis (2DE) resolved the secretome into 57 distinct protein spots. The zymograms developed against 2DE gels identified the presence of three β-glucosidases and five CBHI/EGI isoforms in the secretome. The peptide mass fingerprinting of 17 protein spots by liquid chromatography mass spectrometry characterized the secretome into different glycosyl hydrolase families. The enzyme cocktail produced by A. fumigatus was capable of efficient hydrolysis of alkali pretreated rice straw (at 7% and 10% w/v) resulting in 95% and 91% saccharification, respectively.     

Buffalo Colostrum β-lactoglobulin Inhibits VEGF-Induced Angiogenesis by Interacting with G protein-Coupled Receptor Kinase

β-lactoglobulin (β-lg), a major whey protein was purified and characterised from buffalo colostrum. The in silico analysis of the tryptic peptides based on LC-CID-MS/MS facilitated the identification of protein as β-lg. The sequences IIVTQ f[1–5] and LSFNPTQLEEQCHV f(149–162) of m/z 933⁺ and 851²⁺ were found to match N- and C-extreme of β-lg while IDALNENK f(84–91) and TPEVDDEALEKFDK f(125–138) sequences deduced for m/z 916⁺ and 818²⁺ were in compliance to buffalo milk β-lg. Considering the sequence similarity of β-lg to glycodelin, a proven angiogenic protein, similar role for β-lg from buffalo colostrum (BLG-col) was examined. Interestingly, BLG-col exhibited anti-angiogenic activity by potently inhibiting cell proliferation, micro-vessel sprouting, cell migration and tube formation of human umbilical vein endothelial cells (HUVECs) in a dose-dependent manner but having varied effect on Ehrlich ascites tumor cells, MCF-7, MDA-MB 435 and MDA-MB 231 cell lines. The anti-angiogenic potential of BLG-col was found to be vascular endothelial growth factor mediated. The immunolocalisation of BLG-col on the cell surface of HUVECs evidenced using FITC-labelled β-lg antibody indicated its extra-cellular binding. Furthermore, BLG-col interacting HUVEC membrane protein (64 kDa) was detected by immunoblot and its identity was established by matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry analysis, which showed peptide sequence homology to G protein-coupled receptor kinase 4.     

Enhancement of the stability and temperature range of the mesophases in the binary mixtures of cholesteryl myristate and 4-n-decyloxy benzoic acid

Thermodynamical, optical, and electrical properties of the binary mixtures of cholesteryl myristate (ChM) and 4-n-decyloxybenzoic acid (DOBA) have been carried out by the differential scanning calorimeter, polarized optical microscopy (POM), and impedance spectroscopy. Through thermodynamic study, various phase transition temperatures, transition enthalpies, and transition entropies have been determined to investigate temperature range and stability of the mesophases of the mixtures. Phase diagrams in the heating and cooling cycles have been drawn for the ChM–DOBA binary system. Optical textures of different mesophases have identified with the help of POM. Dielectric permittivity has been determined in planar and homeotropic alignments of the mixtures having DOBA concentrations 30.0 and 92.3 mol %. The experimental dielectric data in the frequency range of 1 Hz to 35 MHz do not show any relaxation mode in both the alignments of these mixtures. Dielectric anisotropy has been determined for the various observed phases of the mixtures.     

Identifying structural–functional analogue of GRL0617, the only well-established inhibitor for papain-like protease (PLpro) of SARS-CoV2 from the pool of fungal metabolites using docking and molecular dynamics simulation

Molecular Diversity - The non-structural protein (nsp)-3 of SARS-CoV2 coronavirus is sought to be an essential target protein which is also named as papain-like protease (PLpro). This protease...     

Fluorescence Investigation of Interactions Between Novel Benzanthrone Dyes and Lysozyme Amyloid Fibrils

A series of novel fluorescent benzanthrone dyes have been tested for their ability to identify and characterize fibrillar aggregates of lysozyme prepared by protein denaturation in concentrated ethanol solution (F_eth) or acidic buffer (F_ac). Quantitative parameters of the dye association with native and fibrillar protein have been derived from the results of fluorimetric titration. The binding characteristics proved to be different for F_eth- and F_ac-bound benzanthrones, highlighting the dye sensitivity to the distinctions in fibril morphology. By comparing the dye preference to fibrillar protein aggregates, AM2, A8 and A6 were selected as the most prospective amyloid tracers. Based on the analysis of red edge excitation shifts and fluorescence lifetimes of the amyloid-bound dyes it was assumed that surface grooves or dry “steric zipper” interface are potential fibril binding sites for the novel fluorophores.     

Computational Study of the Surface‐Enhanced Raman Scattering from Silica‐Coated Silver Nanowires

Surface‐enhanced Raman scattering (SERS) is a popular vibrational spectroscopic technique that can have several applications in chemical and biological sensing. Within the last decade or so, our ability to chemically synthesize nanostructures has improved to the point that the rational design of a variety of SERS substrates is now viable. In this report, we describe a computational study using the finite element method (FEM) to investigate the effects of patchy silica coatings on silver nanowires. We found that varying the degree of silica coating on silver nanowires impacts the enhancement and may be explained through two processes. The first process is a consequence of changes in the dielectric environment surrounding the nanowire due to the silica. As additional layers of silica coat the nanowire, the localized surface plasmon resonance of the nanowire redshifts. The second process is a result of silica distorting the local electric field around the nanowire surface. Anisotropic silica coating can influence anticipated enhancement depending on its spatial localization with respect to excited plasmon modes in the nanowire. We propose that the design of nanostructures with patchy silica coatings can be a viable tool for increasing surface enhancement.