ARTICLE Download: 4| View: 22| Comments: 0
Subject: Chemistry, Organic Chemistry Keywords: secondary metabolites; microbial diversity; metabolomics; molecular network; marine bacteria
Online: 19 October 2019 (02:01:18 CEST)
Rocas Atoll is a unique environment in the Equatorial Atlantic Ocean, hosting a large number of endemic species and studies on the chemical diversity emerging from this biota are rather scarce. Therefore, the present work aims to assess the metabolomic diversity and pharmacological potential of the microbiota from Rocas Atoll. A total of 76 bacteria were isolated and cultured in liquid culture media to obtain crude extracts. About one third (34%) of these extracts were considered cytotoxic against human colon adenocarcinoma HCT-116 cell line. 16S rRNA gene sequencing analysis revealed that the bacteria producing cytotoxic extracts are mainly from the Actinobacteria phylum, including Streptomyces, Salinispora, Nocardiopsis and Brevibacterium genera, and in a smaller proportion from Firmicutes phylum (Bacillus). The search in the GNPS spectral library unveiled a high chemodiversity being produced by these bacteria, including rifamycins, antimycins, desferrioxamines, ferrioxamines, surfactins, surugamides, staurosporine and saliniketals, along with several unidentified compounds. Using an original approach, molecular network successfully highlighted groups of compounds responsible for the cytotoxicity of crude extracts. DEREPLICATOR+, a recently developed in silico tool (GNPS), allowed the identification of derivatives of the macrolide novonestimycin, as the cytotoxic compounds into the extracts produced by Streptomyces BRB-298 and BRB-302. Overall, these results highlighted the pharmacological potential of bacteria from this singular Atoll.
Thu, 17 October 2019
ARTICLE Download: 11| View: 44| Comments: 0 | doi:10.20944/preprints201910.0196.v1
Subject: Chemistry, Applied Chemistry Keywords: kinetic model; dual-wavelength; photopolymerization; spatial confirmation; additive manufacturing; 3d printing
Online: 17 October 2019 (12:33:03 CEST)
The kinetics and modeling of dual-wavelength controlled photopolymerization confinement (PC) are presented and measured data are analyzed by analytic formulas and numerical data. The UV-light initiated inhibition effect is strongly monomer-dependent and different monomers have different C=C bond rate constants and conversion efficacy. Without the UV-light, for a given blue-light intensity, higher initiator concentration (C10) and rate constant (k’) lead to higher conversion, as also predicted by analytic formulas, in which the total conversion rate (RT) is an increasing function of k’R, which is proportional to k[gB1C1]0.5. However, the coupling factor b1 plays a different role that higher b1 leads to higher conversion only in the transient regime; whereas higher b1 leads lower steady-state conversion. For a fixed initiator concentration C10, higher inhibitor concentration (C20) leads to lower conversion due to stronger inhibition effect. However, same conversion reduction was found for the same H-factor of H0 = [b1C10 - b2C20]. Conversion of blue-only are much higher than that of UV-only and UV-blue combined, in which high C20 results a strong reduction of blue-only-conversion, such that the UV-light serves as the turn-off (trigger) mechanism for the purpose of spatial confirmation within the overlap area of UV and blue light. For example, UV-light controlled methacrylate conversion of a glycidyl dimethacrylate resin formulated with a tertiary amine co-initiator, and butyl nitrite, subject to a continuous exposure of a blue light, but an on-off exposure of a UV-light. Finally, we developed a theoretical new finding for the criterion of a good material/candidate governed by a double ratio of light-intensity and concentration, [I20C20.]/[I10C10].
Wed, 16 October 2019
ARTICLE Download: 33| View: 90| Comments: 1
Subject: Chemistry, General & Theoretical Chemistry Keywords: structure prediction; Rosetta; computational modeling; protein design
Online: 16 October 2019 (05:40:52 CEST)
The Rosetta software suite for macromolecular modeling, docking, and design is widely used in pharmaceutical, industrial, academic, non-profit, and government laboratories. Considering its broad modeling capabilities, Rosetta consistently ranks highly when compared to other leading methods created for highly specialized protein modeling and design tasks. Developed for over two decades by a global community of scientists at more than 60 institutions, Rosetta has undergone multiple refactorings, and now comprises over three million lines of code. Here we discuss the methods developed in the last five years, involving the latest protocols for structure prediction, protein–protein and protein–small molecule docking, protein structure and interface design, loop modeling, the incorporation of various types of experimental data, and modeling of peptides, antibodies and other proteins in the immune system, nucleic acids, non-standard amino acids, carbohydrates, and membrane proteins. We briefly discuss improvements to the energy function, user interfaces, and usability of the software. Rosetta is available at www.rosettacommons.org.
ARTICLE Download: 19| View: 75| Comments: 0 | doi:10.20944/preprints201910.0177.v1
Subject: Chemistry, Electrochemistry Keywords: oxide ion conductivity; perovskite oxide; molecular dynamics simulation; ceramics electrolyte
Online: 16 October 2019 (04:55:22 CEST)
The molecular dynamics simulation has been used to investigate the structural and transport properties of (Ba0.5-xSrx)La0.5InO3-δ (x=0, 0.1, 0.2) oxygen-ion conductor. The previous studies reported that the ionic conductivity of Ba-doped LaInO3 decreases because Ba dopant forms narrow oxygen path in the lattice, which could hinder the diffusion of oxygen ion. In this study, we reveal the mechanism to improve the ionic conductivity by Ba and Sr co-doping on La site in LaInO3 perovskite oxide. The results show that the ionic conductivity of (Ba0.5-xSrx)La0.5InO3-δ increases with increasing numbers of Sr ions, which oxygen diffusion paths including Sr ion have larger critical radius than Ba ions. The RDF calculations showed the heights of peak in composition including Sr ions is lower and broaden, so oxygen ions moved easily into other oxygen sites.
ARTICLE Download: 19| View: 71| Comments: 0 | doi:10.20944/preprints201910.0174.v1
Subject: Chemistry, Medicinal Chemistry Keywords: AQP3 protein; molecular docking; molecular dynamics; MM-GBSA analysis; pharmacophore-based filter
Online: 16 October 2019 (04:37:31 CEST)
Aquaporin-3 (AQP3) is one of the aquaglyceroporins, which is expressed in the basolateral layer of the skin membrane. Studies have reported that human skin squamous cell carcinoma overexpresses AQP3 and inhibition of its function may alleviate skin tumorigenesis. In the present study, we have applied a virtual screening method that encompasses filters for physicochemical properties and molecular docking to select potential hit compounds that bind to the Aquaporin-3 protein. Based on molecular docking results, the top 20 hit compounds were analyzed for stability in the binding pocket using unconstrained molecular dynamics simulations and further evaluated for binding free energy. Furthermore, examined the ligand-unbinding pathway of the inhibitor from its bound form to explore possible routes for inhibitor approach to the ligand-binding site. With a good docking score, stability in the binding pocket, and free energy of binding, these hit compounds can be developed as Aquaporin-3 inhibitors in the near future.