Photocatalytic Properties of Silver Nanospherical Arrays Driven by Surface Plasmons

Surface-enhanced Raman scattering (SERS) is a promising technique to study the plasma-driven photocatalytic reactions. Hemispherical alumina nanoarrays with a regular hexagonal arrangement are firstly prepared; then, silver hemispherical nanoarrays are synthesized on the surface of the arrays by silver evaporation. When a laser with a specific wavelength (633 nm) is irradiated on the silver nanoarrays, a large number of regularly arranged local surface plasmon enhancement regions (called “hot spots”) would be generated on its surface. After that, a layer of evenly distributed p-aminothiophenol (PATP) probe molecules was placed on the substrate and the photocatalytic reaction of PATP was driven by the local surface plasmon to form four 4′-di-mercaptoazobenzene (DMAB). Then, under the same experimental conditions, the later product was reversely reacted to form PATP molecule by the action of plasma in the presence of in situ sodium borohydride. SERS can be used to monitor the whole process of the photocatalytic reaction of PATP probe molecules driven by the plasma on the surface of the silver nanoarrays. This research achieves the drawing and erasing of molecular graphics in the micro- and nano-scales, as well as information encryption, reading, and erasing that have strong application value.

Virtual screening on the web for drug repurposing: a primer

We describe a procedure of performing in silico (virtual) screening using a web-based service, the MTiOpenScreen, whichis freely accessible to non-commercial users. We shall use the SARS-CoV-2 main protease as an example. Starting from a structure downloaded from the Protein Data Bank, we discuss how to prepare the coordinates file, taking into account the known biochemical background information of the target protein. The reader will find that this preparation step takes up most of the effort before the target is ready for screening. The steps for uploading the target structure and defining the search volume by critical residues, and the main parameters to use, are outlined. When this protocol is followed, the user will expect to obtain a ranked list of small approved drug compounds docked into the target structure. The results can be readily examined graphically on the web site or downloaded for studying in a local molecular graphics program such as PyMOL.

Scrutinizing Coronaviruses Using Publicly Available Bioinformatic Tools: The Viral Structural Proteins as a Case Study

Since early 2020, the world suffers from a new beta-coronavirus, called SARS-CoV-2, that has devastating effects globally due to its associated disease, Covid-19. Until today, Covid-19, which not only causes life-threatening lung infections but also impairs various other organs and tissues, has killed hundreds of thousands of people and caused irreparable damage to many others. Since the very onset of the pandemic, huge efforts were made worldwide to fully understand this virus and numerous studies were, and still are, published. Many of these deal with structural analyses of the viral spike glycoprotein and with vaccine development, antibodies and antiviral molecules or immunomodulators that are assumed to become essential tools in the struggle against the virus. This paper summarizes knowledge on the properties of the four structural proteins (spike protein S, membrane protein M, envelope protein E and nucleocapsid protein N) of the SARS-CoV-2 virus and its relatives, SARS-CoV and MERS-CoV, that emerged few years earlier. Moreover, attention is paid to ways to analyze such proteins using freely available bioinformatic tools and, more importantly, to bring these proteins alive by looking at them on a computer/laptop screen with the easy-to-use but highly performant and interactive molecular graphics program DeepView. It is hoped that this paper will stimulate non-bioinformaticians and non-specialists in structural biology to scrutinize these and other macromolecules and as such will contribute to establishing procedures to fight these and maybe other forthcoming viruses.

AB0004 THE ASSOCIATION OF THE RARE RS35667974 IFIH1 GENE POLYMORPHISM WITH SIX AUTOIMMUNE DISEASES: STRUCTURAL BIOLOGICAL INSIGHTS

Background:Genome wide association studies (GWAS) have successfully identified novel autoimmune disease-associated loci, with many of them shared by multiple disease-associated pathways but much of the genetics and pathophysiological mechanisms remain still obscure. Considering that most of the potential causal variants are still unknown, many studies showed that the missense variant rs35667974 at interferon induced with helicase C domain 1 (IFIH1) gene is protective for type 1 diabetes (T1D), psoriasis (PS) and psoriatic arthritis (PsA), while it was found to be also associated with ankylosing spondylitis (AS), Crohn’s disease (CD) and ulcerative colitis (UC). IFIH1 gene encodes a cytoplasmic RNA helicase that recognizes viral RNA and is involved in innate immunity through recognition of viral RNA [1].Objectives:To investigate the role of the rare rs35667974 variant of IFIH1 gene, which resides in exon 14 and changes a conserved isoleucine at position #923 to valine in T1D, PS, PsA, AS, CD and UC [2-4] as well as the mechanism that may affect the function in the protein structure.Methods:Evolutionary analysis revealed heavily conserved sequence elements among species, indicating structural/functional importance of the mutation at position #923. In silico mutagenesis and three-dimensional (3D) homology modeling was used to localize the polymorphism under study on the IFIH1 protein. The mutant was constructed using molecular modeling with the program Maestro (Schrodinger, LLC) [5]. Molecular mechanics/dynamics studies were applied to validate structural/functional changes caused by the Ile923V substitution. All figures depicting 3D models were generated using the PyMOL molecular-graphics system V.2.2 [6].Results:Evolutionary and structural analysis revealed that the position of residue Ile923 is located on a protein loop (921-927) directly interacting with mRNA both to the phosphoribose chain and the base pairs. Mutation of Ile to Val at position #923 will directly affect the said interaction with mRNA [7] (Figure 1). Moreover, it has been reported that pre-mRNA or mRNA levels did not correlate with Ile923Val, suggesting that, Ile923Val did not alter the expression of IFIH1 in a major way [7].Figure 1.Structural representation of the interferon-induced helicase C domain-containing protein 1 [Homo sapiens] structure (4GL2 from Protein Data Bank) (in green) bound to the double stranded RNA (in orange-yellow). The location of the mutation (I923V) is highlighted in pink. The proximity of the aminoacid 923 to the nucleotide is apparent.Conclusion:This study represents a comprehensive evaluation of the role of the shared rs35667974 variant of autoimmune locus IFIH1, reported to lead to a loss of function phenotype and, as a consequence, reduced levels of IFIH1 protein and activity that protect against autoimmunity. Structural analysis of rare shared genetic susceptibility or protection loci may provide insight to our understanding of the pathophysiology of autoimmune diseases and the research findings may affect the better management of the diseases under study.References:[1]Nejentsev S et al. (2009). Science 324:387–389.[2]Smyth DJ et al. (2006). Nat Genet. 38: 617–619.[3]Li Y et al. (2010). J Invest Dermatol 130:2768–2772.[4]Ellinghaus D et al. (2016). Nat Genet 48:510–518.[5]Schrödinger Release 2017-1: Maestro, Schrödinger, LLC, New York, NY, 2017.[6]Schrödinger LLC: The PyMOL Molecular Graphics System 2016 version 2.2.[7]Wu B et al. (2013). Cell 152:276-289[8] Downes K et al. (2010). PLoS One 5:e12646.Disclosure of Interests:None declared

Effect of Alkali Atom Doping on the Electronic Structure and Aromatic Character of Planar and Quasi-Planar Al13+ Clusters

A set of three Al13+ clusters, one perfectly planar and two quasi-planar structures have been recently reported by our group [Guin et. al. Journal of Molecular Graphics and Modeling, 2020, 97, 107544]. One of the quasi-planar structures is true minima (GS) with zero imaginary frequency and another one is transition state structure (TS) with one imaginary frequency, whereas the perfectly planar structure has three imaginary frequencies. All three posses bilaterally symmetry with identical structural features - a set of ten aluminium atoms encircle a triangular core and also this set of three aluminium cluster is a rare example of a metallo-aromatic system in which highly anti-aromatic islands are embedded in an aromatic sea. One of the atoms of the central triangle lies on the symmetry axis and is crucial for the stability of these clusters. In the present study, we have explored the effect of doping alkali atoms (Li, Na and K) at this pivotal site of the cluster with an aim to understand the structural stability and the effect on the aromatic character as compared to the parent clusters. Besides the electronic structural analysis, NICS and ELF studies have also been carried out to characterize the aromatic nature of the doped clusters. Interestingly it has been found that even with the incorporation of the alkali atoms the bilateral symmetry of the clusters remains intact but instead of the central position the alkali atoms drift towards the periphery of the cluster along the symmetry line and equilibrate on the periphery. The dipole moment of the clusters systematically increases and the overall aromaticity of the cluster systematically decreases with the increase in the atomic number of the dopant alkali atoms.

A molecular dynamic study of Soil Organic Matter stabilization mechanisms

<p>It is well known that some fractions of soil organic matter (SOM) can resist to physical and (bio)chemical degradation which can be attributed to factors ranging from molecular properties to the preference for digesting other molecular species by microorganisms. Some mechanisms, by which organic matter is protected, are often referred to as: physical stabilization through microaggregation, chemical stabilization by formation of SOM-mineral aggregates, and biochemical stabilization through the formation of recalcitrant SOM.</p><p>Protection mechanisms are responsible for the accumulation process of organic carbon, reducing the exposure of organic matter and making it less vulnerable to microbial, enzymatic or chemical attacks. In these mechanisms, water molecular bridges and metal cation bridges play a key role. Cation bridges serve as aggregation sites on humic substances, forming dense matter, in comparison to systems where bridges are missing. This effect is enhanced in systems with cations at higher oxidation states.</p><p>By using the modeler tool developed in our group (Vienna Soil–Organic–Matter Modeler, VSOMM2) (Escalona et al., 2021), we generated aggregate models of humic substances at atomistic scale reflecting the diversity in composition, size and conformations of the constituting molecules. Further, we built models of organo-clay aggregates using kaolinite and montmorillonite as typical soil minerals. This allowed a systematic study to understand the effect of the surrounding environment at microscopic scale, not fully accessible experimentally.</p><p>Molecular simulations of the adsorption process of SOM aggregates on the reactive surfaces of led to two observations: 1) the humic substances aggregates were able to interact with the reactive surfaces mainly via hydrogen bonds forming stable organic matter-clay complexes and 2) the aggregates subsequently lost rigidity and stability after metal cations removing, consequently leading to a gradual loss of humic substance molecules, evidencing the role of metal cations in the protection mechanism of soil organic matter aggregates and possibly explaining its recalcitrance (Galicia-Andrés et al., 2021).</p><p>References</p><ul><li>Escalona, Y., Petrov, D., & Oostenbrink, C. (2021). Vienna soil organic matter modeler 2 (VSOMM2). Journal of Molecular Graphics and Modelling, 103, 107817. https://doi.org/10.1016/j.jmgm.2020.107817</li> <li>Galicia-Andrés, E., Grančič, P., Gerzabek, M. H., Oostenbrink, C., & Tunega, D. (2021). Modeling of interactions in natural and synthetic organoclays. In I. C. Sainz Diaz (Ed.), Computational modeling in clay mineralogy.</li> </ul>

Epitope Mapping of Exposed Tegument and Alimentary Tract Proteins Identifies Putative Antigenic Targets of the Attenuated Schistosome Vaccine

The radiation-attenuated cercarial vaccine remains the gold standard for the induction of protective immunity against Schistosoma mansoni. Furthermore, the protection can be passively transferred to naïve recipient mice from multiply vaccinated donors, especially IFNgR KO mice. We have used such sera versus day 28 infection serum, to screen peptide arrays and identify likely epitopes that mediate the protection. The arrays encompassed 55 secreted or exposed proteins from the alimentary tract and tegument, the principal interfaces with the host bloodstream. The proteins were printed onto glass slides as overlapping 15mer peptides, reacted with primary and secondary antibodies, and reactive regions detected using an Agilent array scanner. Pep Slide Analyzer software provided a numerical value above background for each peptide from which an aggregate score could be derived for a putative epitope. The reactive regions of 26 proteins were mapped onto crystal structures using the CCP4 molecular graphics, to aid selection of peptides with the greatest accessibility and reactivity, prioritizing vaccine over infection serum. A further eight MEG proteins were mapped to regions conserved between family members. The result is a list of priority peptides from 44 proteins for further investigation in multiepitope vaccine constructs and as targets of monoclonal antibodies.

A virtual alternative to molecular model sets: a beginners’ guide to constructing and visualizing molecules in open-source molecular graphics software

Objective The application of molecular graphics software as a simple and free alternative to molecular model sets for introductory-level chemistry learners is presented. Results Based on either Avogadro or IQmol, we proposed four sets of tasks for students, building basic molecular geometries, visualizing orbitals and densities, predicting polarity of molecules and matching 3D structures with bond-line structures. These topics are typically covered in general chemistry for first-year undergraduate students. Detailed step-by-step procedures are provided for all tasks for both programs so that instructors and students can adopt one of the two programs in their teaching and learning as an alternative to molecular model sets.