Stillingkjellerup5633

The current COVID-19 outbreak warrants the design and development of novel anti-COVID therapeutics. Using a combination of bioinformatics and computational tools, we modelled the 3D structure of the RdRp (RNA-dependent RNA polymerase) of SARS-CoV2 (severe acute respiratory syndrome coronavirus-2) and predicted its probable GTP binding pocket in the active site. GTP is crucial for the formation of the initiation complex during RNA replication. This site was computationally targeted using a number of small molecule inhibitors of the hepatitis C RNA polymerase reported previously. Further optimizations suggested a lead molecule that may prove fruitful in the development of potent inhibitors against the RdRp of SARS-CoV2.Optimizing the aging process is urgently required in the distilled spirit industry because of the time-consuming and expensive procedure of natural aging. Herein, the componential changes of the liquor sample are confirmed by the component analysis (e.g., gas chromatograph), and the effect of electrochemical oxidization treatment on the overall properties of typical Chinese liquor (Baijiu) is investigated. The key finding is that high oxidative potential can be used to catalyze the oxidation of alcohols, and the reaction rate is dramatically faster than that in the process of natural aging. The present study reveals the influence of electrochemical oxidation on the contents of compounds (particularly, the alcohols) in Baijiu and offers a perspective into the utilization of electrochemical oxidization treatment as an alternative strategy for artificial maturation of Baijiu.In this paper, we demonstrate through examples how the concept of a Semantic Web based knowledge graph can be used to integrate combustion modeling into cross-disciplinary applications and in particular how inconsistency issues in chemical mechanisms can be addressed. We discuss the advantages of linked data that form the essence of a knowledge graph and how we implement this in a number of interconnected ontologies, specifically in the context of combustion chemistry. Central to this is OntoKin, an ontology we have developed for capturing both the content and the semantics of chemical kinetic reaction mechanisms. PF 429242 OntoKin is used to represent the example mechanisms from the literature in a knowledge graph, which itself is part of the existing, more general knowledge graph and ecosystem of autonomous software agents that are acting on it. We describe a web interface, which allows users to interact with the system, upload and compare the existing mechanisms, and query species and reactions across the knowledge graph. The utility of the knowledge-graph approach is demonstrated for two use-cases querying across multiple mechanisms from the literature and modeling the atmospheric dispersion of pollutants emitted by ships. As part of the query use-case, our ontological tools are applied to identify variations in the rate of a hydrogen abstraction reaction from methane as represented by 10 different mechanisms.Molecular recognition features (MoRFs) are common in intrinsically disordered proteins (IDPs) and intrinsically disordered regions (IDRs). MoRFs are in constant order-disorder structural transitions and adopt well-defined structures once they are bound to their targets. Here, we study Escargot (Esg), a transcription factor in Drosophila melanogaster that regulates multiple cellular functions, and consists of a disordered N-terminal domain and a group of zinc fingers at its C-terminal domain. We analyzed the N-terminal domain of Esg with disorder predictors and identified a region of 45 amino acids with high probability to form ordered structures, which we named S2. Through 54 μs of molecular dynamics (MD) simulations using CHARMM36 and implicit solvent (generalized Born/surface area (GBSA)), we characterized the conformational landscape of S2 and found an α-MoRF of ∼16 amino acids stabilized by key contacts within the helix. To test the importance of these contacts in the stability of the α-MoRF, we evaluated the effect of point mutations that would impair these interactions, running 24 μs of MD for each mutation. The mutations had mild effects on the MoRF, and in some cases, led to gain of residual structure through long-range contacts of the α-MoRF and the rest of the S2 region. As this could be an effect of the force field and solvent model we used, we benchmarked our simulation protocol by carrying out 32 μs of MD for the (AAQAA)3 peptide. The results of the benchmark indicate that the global amount of helix in shorter peptides like (AAQAA)3 is reasonably predicted. Careful analysis of the runs of S2 and its mutants suggests that the mutation to hydrophobic residues may have nucleated long-range hydrophobic and aromatic interactions that stabilize the MoRF. Finally, we have identified a set of residues that stabilize an α-MoRF in a region still without functional annotations in Esg.Human leukocyte antigens (HLAs) play a critical role in human-acquired immune responses by the recognition of non-self-peptides derived from exogenous bacteria, fungi, virus, and so forth. The accurate prediction of HLA-binding peptides is thus extremely useful for the mechanistic research of cell-mediated immunity and related epitope-based vaccine design. In this work, a simple pan-specific gated recurrent unit (GRU)-based recurrent neural network model was successfully proposed for predicting HLA-I-binding peptides. In comparison with the available six allele-specific, four pan-specific, and two ensemble-based prediction models, the GRU model achieves the highest area under the receiver operating characteristic curve (AUC) scores for 21 of 64 entries of the test benchmark datasets. Besides, the GRU model also achieves satisfactory performance on other 24 entries, of which the AUC scores differ by less than 0.1 from the highest scores. Overall, taking the advantages of the GRU network and auto-embedding techniques into account, the established pan-specific GRU model is more simple and direct and shows satisfactory prediction performance for HLA-I-binding peptides with varying lengths.