FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2952480964> ?p ?o ?g. }

• W2952480964 abstract "In the field of synthetic biology, highly interdisciplinary approaches for thedesign and modelling of functional molecules using computer-assisted methodshave become established in recent decades. These computer-assisted methods aremainly used when experimental approaches reach their limits, as computer modelsare able to e.g., elucidate the temporal behaviour of nucleic acid polymers orproteins by single-molecule simulations, as well as to illustrate the functionalrelationship of amino acid residues or nucleotides to each other. The knowledgeraised by computer modelling can be used continuously to influence the furtherexperimental process (screening), and also shape or function(rational design) of the considered molecule. Such an optimization of thebiomolecules carried out by humans is often necessary, since the observedsubstrates for the biocatalysts and enzymes are usually synthetic (``man-madematerials'', such as PET) and the evolution had no time to provide efficientbiocatalysts.With regard to the computer-aided design of single-molecules, two fundamental paradigmsshare the supremacy in the field of synthetic biology. On the one hand,probabilistic experimental methods (e.g., evolutionary design processes such asdirected evolution) are used in combination with High-ThroughputScreening (HTS), on the other hand, rational, computer-aided single-molecule designmethods are applied.For both topics, computer models/concepts were developed, evaluated andpublished.The first contribution in this thesis describes a computer-aided design approachof the Fusarium Solanie Cutinase (FsC). The activity loss of the enzyme during alonger incubation period was investigated in detail (molecular) with PET. Forthis purpose, Molecular Dynamics (MD) simulations of the spatial structure ofFsC and a water-soluble degradation product of thesynthetic substrate PET (ethylene glycol) were computed. The existing model wasextended by combining it with Reduced Models. This simulation study hasidentified certain areas of FsC which interact verystrongly with PET (ethylene glycol) and thus have a significant influence on theflexibility and structure of the enzyme.The subsequent original publication establishes a new method for the selectionof High-Throughput assays for the use in protein chemistry. The selection ismade via a meta-optimization of the assays to be analyzed. For this purpose,control reactions are carried out for the respective assay. The distance of thecontrol distributions is evaluated using classical static methods such as theKolmogorov-Smirnov test. A performance is then assigned to each assay. Thedescribed control experiments are performed before the actual experiment(screening), and the assay with the highest performance is used for furtherscreening. By applying this generic method, high success rates can be achieved. We were able to demonstrate this experimentally usinglipases and esterases as an example.In the area of green chemistry, the above-mentioned processes can be useful for findingenzymes for the degradation of synthetic materials more quickly or modifying enzymes that occur naturally in such a way that these enzymes canefficiently convert synthetic substrates after successful optimization. For thispurpose, the experimental effort (consumption of materials) is kept to a minimumduring the practical implementation. Especially for large-scale screenings, aprior consideration or restriction of the possible sequence-space can contribute significantly to maximizing the success rate of screenings and minimizing the totaltime they require.In addition to classical methods such as MD simulations in combination withreduced models, new graph-based methods for the presentation and analysis of MDsimulations have been developed. For this purpose, simulations were convertedinto distance-dependent dynamic graphs. Based on this reduced representation,efficient algorithms for analysis were developed and tested. In particular,network motifs were investigated to determine whether this type ofsemantics is more suitable for describing molecular structures and interactionswithin MD simulations than spatial coordinates. This concept was evaluated forvarious MD simulations of molecules, such as water, synthetic pores, proteins,peptides and RNA structures. It has been shown that this novel form of semanticsis an excellent way to describe (bio)molecular structures and their dynamics.Furthermore, an algorithm (StreAM-Tg) has been developed for the creation ofmotif-based Markov models, especially for the analysis of single moleculesimulations of nucleic acids. This algorithm is used for the design of RNAs. Theinsights obtained from the analysis with StreAM-Tg (Markov models) canprovide useful design recommendations for the (re)design of functional RNA.In this context, a new method was developed to quantify the environment (i.e.water; solvent context) and its influence on biomolecules in MD simulations. Forthis purpose, three vertex motifs were used to describe the structure of theindividual water molecules. This new method offers many advantages. With thismethod, the structure and dynamics of water can be accurately described. Forexample, we were able to reproduce the thermodynamic entropy of water in theliquid and vapor phase along the vapor-liquid equilibrium curve from thetriple point to the critical point.Another major field covered in this thesis is the development of newcomputer-aided approaches for HTS for the design offunctional RNA. For the production of functional RNA (e.g., aptamers and riboswitches), an experimental,round-based HTS (like SELEX) is typically used. By usingNext Generation Sequencing (NGS) in combination with the SELEX process,this design process can be studied at the nucleotide and secondary structurelevels for the first time. The special feature of small RNA molecules comparedto proteins is that the secondary structure (topology), with a minimum freeenergy, can be determined directly from the nucleotide sequence, with a highdegree of certainty.Using the combination of M. Zuker's algorithm, NGS and the SELEX method, it waspossible to quantify the structural diversity of individual RNA molecules underconsideration of the genetic context. This combination of methods allowed theprediction of rounds in which the first ciprofloxacin-riboswitch emerged.In this example, only a simple structural comparison was made for thequantification (Levenshtein distance) of the diversity of each round. To improve this, a new representation of the RNA structure as a directed graphwas modeled, which was then compared with a probabilistic subgraph isomorphism.Finally, the NGS dataset (ciprofloxacin-riboswitch) was modeled as a dynamicgraph and analyzed after the occurrence of defined seven-vertex motifs. For thispurpose, motif-based semantics were integrated into HTSfor RNA molecules for the first time. The identified motifs could be assigned tosecondary structural elements that were identified experimentally in theciprofloxacin aptamer R10k6.Finally, all the algorithms presented were integrated into an R library,published and made available to scientists from all over the world." @default.
• W2952480964 created "2019-06-27" @default.
• W2952480964 creator A5010048143 @default.
• W2952480964 date "2019-01-01" @default.
• W2952480964 modified "2023-09-24" @default.
• W2952480964 title "Development of Computer-aided Concepts for the Optimization of Single-Molecules and their Integration for High-Throughput Screenings" @default.
• W2952480964 hasPublicationYear "2019" @default.
• W2952480964 type Work @default.
• W2952480964 sameAs 2952480964 @default.
• W2952480964 citedByCount "0" @default.
• W2952480964 crossrefType "dissertation" @default.
• W2952480964 hasAuthorship W2952480964A5010048143 @default.
• W2952480964 hasConcept C104317684 @default.
• W2952480964 hasConcept C127413603 @default.
• W2952480964 hasConcept C14036430 @default.
• W2952480964 hasConcept C143065580 @default.
• W2952480964 hasConcept C154945302 @default.
• W2952480964 hasConcept C171250308 @default.
• W2952480964 hasConcept C183696295 @default.
• W2952480964 hasConcept C185592680 @default.
• W2952480964 hasConcept C191908910 @default.
• W2952480964 hasConcept C192562407 @default.
• W2952480964 hasConcept C2908542902 @default.
• W2952480964 hasConcept C41008148 @default.
• W2952480964 hasConcept C49853544 @default.
• W2952480964 hasConcept C49937458 @default.
• W2952480964 hasConcept C53105671 @default.
• W2952480964 hasConcept C55493867 @default.
• W2952480964 hasConcept C70721500 @default.
• W2952480964 hasConcept C78458016 @default.
• W2952480964 hasConcept C86803240 @default.
• W2952480964 hasConcept C9418097 @default.
• W2952480964 hasConceptScore W2952480964C104317684 @default.
• W2952480964 hasConceptScore W2952480964C127413603 @default.
• W2952480964 hasConceptScore W2952480964C14036430 @default.
• W2952480964 hasConceptScore W2952480964C143065580 @default.
• W2952480964 hasConceptScore W2952480964C154945302 @default.
• W2952480964 hasConceptScore W2952480964C171250308 @default.
• W2952480964 hasConceptScore W2952480964C183696295 @default.
• W2952480964 hasConceptScore W2952480964C185592680 @default.
• W2952480964 hasConceptScore W2952480964C191908910 @default.
• W2952480964 hasConceptScore W2952480964C192562407 @default.
• W2952480964 hasConceptScore W2952480964C2908542902 @default.
• W2952480964 hasConceptScore W2952480964C41008148 @default.
• W2952480964 hasConceptScore W2952480964C49853544 @default.
• W2952480964 hasConceptScore W2952480964C49937458 @default.
• W2952480964 hasConceptScore W2952480964C53105671 @default.
• W2952480964 hasConceptScore W2952480964C55493867 @default.
• W2952480964 hasConceptScore W2952480964C70721500 @default.
• W2952480964 hasConceptScore W2952480964C78458016 @default.
• W2952480964 hasConceptScore W2952480964C86803240 @default.
• W2952480964 hasConceptScore W2952480964C9418097 @default.
• W2952480964 hasLocation W29524809641 @default.
• W2952480964 hasOpenAccess W2952480964 @default.
• W2952480964 hasPrimaryLocation W29524809641 @default.
• W2952480964 hasRelatedWork W1573877174 @default.
• W2952480964 hasRelatedWork W1750473576 @default.
• W2952480964 hasRelatedWork W1850500669 @default.
• W2952480964 hasRelatedWork W199132350 @default.
• W2952480964 hasRelatedWork W2002141822 @default.
• W2952480964 hasRelatedWork W2020546070 @default.
• W2952480964 hasRelatedWork W2026461419 @default.
• W2952480964 hasRelatedWork W2045709175 @default.
• W2952480964 hasRelatedWork W205224400 @default.
• W2952480964 hasRelatedWork W2071256770 @default.
• W2952480964 hasRelatedWork W2080026723 @default.
• W2952480964 hasRelatedWork W2148339059 @default.
• W2952480964 hasRelatedWork W2154515666 @default.
• W2952480964 hasRelatedWork W2247716574 @default.
• W2952480964 hasRelatedWork W2293107922 @default.
• W2952480964 hasRelatedWork W2315378705 @default.
• W2952480964 hasRelatedWork W3012765374 @default.
• W2952480964 hasRelatedWork W3211688917 @default.
• W2952480964 hasRelatedWork W70582889 @default.
• W2952480964 hasRelatedWork W74635577 @default.
• W2952480964 isParatext "false" @default.
• W2952480964 isRetracted "false" @default.
• W2952480964 magId "2952480964" @default.
• W2952480964 workType "dissertation" @default.