Structure Modification in Chemical Databases

Drug molecules frequently contain functional groups such as amines and carboxylic acids that are ionized under normal physiological conditions. Typically, these are registered in databases in their neutral forms that are perfectly reasonable when the main objective is efficient retrieval of structures. Representation of tautomers [6, 7], which differ only in bond type and hydrogen atom connectivity, raises similar issues while measurement of the relevant equilibrium constants is significantly more difficult. 

Normally, programs for virtual screening, for example, docking software, do not take multiple hydrogen placements of these three types into account. There are, however, a few partial solutions. The docking program FlexX [11] can generate stereoisomers on 

Recently, two more approaches that will add similar preprocessing functionality to commercial virtual screening software have been reported [13,14]. 

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Kenny, P.W. and Sadowski, (. (2004) Structure modification in chemical databases, in Chemoinformatics in Drug Discovery (ed. T.I. Oprea), Wiley-VCH Verlag GmbH, Weinheim, pp. 271-285. 

Keimy PW, Sadowski J. Structure modification in chemical databases. Methods Princ Med Chem 2005 23 271-285. 

The modification of data already on file is accomplished in a somewhat similar manner. The information in the database is first retrieved through one of the query methods and then altered. In the case of invalid data or an unplausable chemical structure, MAECIS also contains a delete function. MAECIS creates and maintains for the user all of the necessary cross-references between the associated data files. 

Cleaning and Transforming Data. When importing data from diverse data sources (files, databases, spreadsheets, LIMS systems, etc.) into a database or data warehouse, the 4 ta usually needs to be standardized, checked, and sometimes transformed to some common format and content. This allows faster search and retrieval, and serves as a check of data integrity. The rules that define the cleaning/trans-formation process are often termed "business rules," and in the case of chemical data, they may include checking and modification of chemical structures. 

The science community has clearly established the essential role which protein and DNA sequences play in the understanding of biological systems. The sequences themselves are informative Indeed, many software tools are available which allow to make sense of the primary sequence information. Take those that analyse protein sequences for domains and active sites, perform similarity and homology searches, or predict the three-dimensional structure or physico-chemical parameters. However, raw sequences contain insufficient information, per se. One cannot infer any description or understanding of the level of expression of the active proteins, the content of post-translational modifications (PTMs), the tertiary structure and, what is perhaps the most relevant information, a protein s function. Like the sequences themselves, all these added value data need to be captured in various databases. These databases have to be queried by different types of users in proteomics and should therefore be easily searchable by software tools and be inter-linked in order to document the correspondences between the type of information provided by the different databases. 

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