Structure databases components

Today, pharmaceutical companies are linking CDS to business systems such as SAP, chemical structure databases, electronic laboratory notebooks, and corporate data warehousing solutions. Many commonly used software products utilize COM Automation (Microsoft s Component Object Model) to provide a powerful array of programmable objects that allow seamless connections between applications. 

Fig. 8.2 Extraction of components from corporate structural database.

The search is then performed using components extracted from the user s structural database. Again, granting the user the ability to govern the source of the components is key. Perhaps a database of known inhibitors can be utilized - further enriching the source components for potential solutions. After several minutes, potential derivatives are generated. These initial structures can be analyzed and evaluated for undesired chemical assemblies. The chemical descriptors can then be modified to eliminate such structures and enrich for preferred compounds. Sample hits are shown in Figure 8.18. 

ChemSelect AQB (Advanced Query Builder) A Pfizer in-house developed reusable Java component that allows users to query various molecular structure databases within Pfizer based on molecular structural information and/or other properties, retrieve, manage, and export retrieved hits. It has a functional role similar to MDL ISIS/BASE, but with many enhanced capabilities. PGVL Hub has embedded this reusable Java component within itself so that users can search for suitable reactants from various corporate reactants databases and inventory houses and return the hits seamlessly back into PGVL Hub design session. From user s point of view, the ChemSelect AQB component is just part of PGVL Hub. 

The chemical structure database and registration procedure play dual roles in an enterprise screening informatics environment. These components are essential to the transactional HTS informatics system and serve as the basis for cheminformatics data analysis. While capturing the chemical structures for association with the final screening endpoints, this system also captures and applies the organizational chemical business rules to validate and standardize chemical structures and canonicalize their representations. Structural representation is a critical prerequisite for any subsequent cheminformatics analysis. 

Throughout this chapter, reference will be made to techniques and approaches described elsewhere in this book, and a certain familiarity with these topics will be assumed Methods of representing molecular conformation, and different coordinate systems (Chapter 1), ways of dealing with symmetry aspects (Chapter 2), data retrieval from the Cambridge Structural Database (CSD Chapter 3) [3], and multivariate statistical techniques such as principal component analysis (PCA) and cluster analysis (CA Chapter 4). 

Sequence databases generally specialize in one type of sequence data, i.e. DNA, RNA or protein (Higgins and Taylor, 2(XX)). Structure data must unambiguously define the atomic connectivities and the precise three-dimensional coordinates of all atoms within the molecule. These sequences and structures are the itans to be eomputed on and worked with as the valuable components of the primary databases. Generally, the gateways to sequence and structure databases include ... 

Figure 1 shows a schema for an ideal distributed chemical information system. Several authors in this book refer to the need for standard interfaces. Ultimately, the personal computer will provide the graphics interface not only to personal computer databases but also to company databases running on the company mainframe, and possibly also through the same network to public hosts, so that the chemist using a personal workstation will be able to create queries which can be addressed to local files, company files and public files. Soon, chemical databases will be available on Compact Disk Read Only Memory (CD-ROM) searchable by both substructure and text. These too fit into the scheme of Figure 1. Databases such as infra-red spectra libraries will have structure-searchable components either on the personal computer or on the laboratory instrument and will also be used through the same graphical interface.

The problem of risk analysis in pipelines, especially to be treated imder a focus of Decision Theory, Utility Theory and the Multi-Attribute Utility Theory (MAUT), requires a decision support system with a very much rich computational capacity in all its components. The Decision Support System for Risk Analysis in installation of pipelines imder a MAUT approach should, at the same time, have substantial databases and models that meet the needs of the mathematical modeling to the problem, and a structured dialogue component to perform an intense communication with the decision-maker. 

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