Workflow Examples

Workflow for filtering compounds using element filter (Figs. 9.17 and 9.18) 

NOTE Sample workflows can be downloaded from the following links 

9 Integration of Automated Workflow in Chemoinformatics for Drug Discovery 

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FIGURE 11.1 As is workflow example diagram for manual sample dilution. 

FIGURE 11.2 To be workflow example for an automated sample dilutor. 

Both ligand- and structure-based methods can be applied in virtual screening. An example of a workflow chart for virtual screening is depicted in Figure 10,4-3. 

Table 5 Workflows that provide examples of the combined use of methods... 

In our laboratories, a cycle time of 90 sec can be achieved with a dilution factor of 1 25 for a given sample concentration, allowing the purity and identity control of two and a half 384-well microtiter plates per day. The online dilution eliminated an external step in the workflow and reduced the risks of decomposition of samples in the solvent mixture (weakly acidic aqueous solvent) required for analysis. Mao et al.23 described an example in which parallel sample preparation reduced steps in the workflow. They described a 2-min cycle time for the analysis of nefazodone and its metabolites for pharmacokinetic studies. The cycle time included complete solid phase extraction of neat samples, chromatographic separation, and LC/MS/MS analysis. The method was fully validated and proved rugged for high-throughput analysis of more than 5000 human plasma samples. Many papers published about this topic describe different methods of sample preparation. Hyotylainen24 has written a recent review. 

The previous chapters have dealt mainly with LC/MS analysis involving short run times, many samples, and relatively small numbers of compounds in samples. What about samples containing very complex compound mixtures, for example, natural products, samples from biomarker discovery, protein digests, and QA/QC method development or metabolite identification samples requiring detection of every component Such workflows often require several analysis steps with different columns and different mobile phases and pH values to increase the separation probability by changing the selectivities of individual runs. 

In this case study we have not adopted any particular component architecture such as Cat One (see Section 10.8.1, Cat One An Example Component Architecture). So our connectors have been limited to standard requests or responses between large-grained components rather than higher-level facilities such as events, properties, and workflow transfers. 

Aiming to construct explicit dynamic models, Eqs. (5) and (6) provide the basic relationships of all metabolic modeling. All current efforts to construct large-scale kinetic models are based on an specification of the elements of Eq (5), usually involving several rounds of iterative refinement For a schematic workflow, see again Fig. 4. In the following sections, we provide a brief summary of the properties of the stoichiometric matrix (Section III.B) and discuss the most common functional form of enzyme-kinetic rate equations (Section III.C). A selection of explicit kinetic models is provided in Table I. TABLE I Selected Examples of Explicit Kinetic Models of Metabolisin 1 ... 

To illustrate the parameterization and the workflow of SKM more clearly, we briefly consider a simple example. The simplest possible metabolic network consists of r = 2 reactions and m = 1 metabolite... 

Bigure 16.5 summarizes our approach to using validated QSAR models for virtual screening as applied to the anticonvulsant dataset. It presents a practical example of the drug discovery workflow that can be generalized for any dataset in which sufficient data to develop reliable QSAR models is available. 

Once the robotic system and procedure passed the optimization and reproducibility tests for a certain type of reaction, the researcher has the chance to move on to the most delightful part of a high-throughput experimentation workflow that is to follow the reaction kinetics of the reaction by withdrawing several samples under comparable conditions. The characterization of these samples allows the determination of the apparent rate constants and activation energies in a very reproducible way. As an example, the anionic polymerization of St in cyclohexane initiated by i-BuLi under different reaction conditions was investigated. Several samples were withdrawn during the reaction into small vials which were prefllled with 25 pL of... 

To illustrate the power of integrated workflows consisting of primary and secondary screening technologies we briefly describe two examples from our own laboratories. 

The 48-channel MCFB reactor and the catalyst synthesis workflow components were similarly validated in experiments where bulk samples were prepared in library format, screened in the array format, and the data compared with known examples. This part of the workflow was used for initial hit validation and to opti-... 

High-Throughput Workflow Development Strategies and Examples in Heterogeneous Catalysis... 

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