Substructures Searching Handling

The information retrieval in MAECIS is accomplished using one of three available commands SHOW, FIND, or SEARCH. The SHOW command is the simplest one to use and requires only a code number or registry number. It allows the user to retrieve all chemical structures and associated information stored under a particular code number. In most cases this fulfills the user s needs. The FIND command is used for complex searches involving various combinations of multiple data fields, handles substructure searching. Queries such structures with a molecular weight between 200 and 250 containing an ester substructure" are handled by the FIND command. Finally, the SEARCH command is used for chemical structure searches. This search takes only seconds and allows the chemist to determine if a particular molecule is already in the database. 

The identification and evaluation of the similarity of chemical structures in an objective and quantitative way is one of goals of chemical structure handling by computer. Conventionally, the problem of structural similarity of chemical compounds has been solved by chemists in an essentially intuitive way based on visual perception. The methods discussed herein are different from conventional substructure search technique. As already stated, the problem of computer handling of chemical structures is not only of the utmost importance in attempts... 

SLN includes support for substructure search queries. In the SMILES world, this task is handled by other derived formats. 

These topographical systems record the structural information more explicitly than the earlier methods, and so allow greater flexibility in substructure searching. They are, however, very expensive in terms of storage space, and they are specifically a product of the computer age since it is only with the advent of the computer that the ability to handle the necessarily large and complex files has become available. Progress in this field has recently been reviewed 5i.52) ... 

R. D. Brown, G. M. Downs, G. Jones, and P. Willett, /. Chem. Inf. Comput. Set., 34, 47 (1994). Hyperstructure Model for Chemical Structure Handling Techniques for Substructure Searching. 

When these were examined against our existing system (INDABS), it became clear that a radical re-design of our database structure was going to be necessary and that a graphical structure handling module had to be acquired or written in-house. Our substructure search system also had to be rewritten because structures and chemical searches entered graphically would be stored as connection tables instead of WLN. 

An extension of SOCRATES to handle chemical reactions, called CONTRAST, has also been developed at Sandwich, again with some collaboration from Peter Willett at Sheffield. In SOCRATES the precursors of our company compounds are stored in the compound registry file, and so application of a reaction site detection algorithm to the starting material and product generates a set of modified connection tables and fragment screens, and a set ofreaction bit-screens. The substructure search graphical structure input menu was modified to enable the chemist to identify the atoms involved in the reaction, but otherwise is essentially the same interface as in SOCRATES. 

The structures of the Beilstein compounds are stored in connection tables (CT s) to allow a very flexible structure and substructure search. Since most commercially available structure/substructure handling programs such as MACCS (MDL) or DARC (Telesystemes/Questel) work on the basis of CT s, the Beilstein Registry Connection Table (BRCT) can be easily adapted for in-house systems. 

The above considerations concern atom-by-atom substructure searches, which in practice are only the final steps of a substructure query handling cycle since, usually, some screening steps are utilised to substantially narrow down the number of potential hits. Only the relatively few hit candidates are then subject to atom-by-atom searches. It is worth considering the effects of such screening on the expected comparative performance of sequentially performed versus h3q>erstructure based (i.e., quasiparallel) procedures. 

The purpose of adding stereochemistry to Registry connection tables is to make this information available in a form more accessible for computer handling and manipulation. This will permit stereochemical information to be used to enhance structure display and substructure search, both of which currently operate at the topological level. In the case of substructure search, the addition of stereochemical capabilities implies that the user could specify a query with stereochemistry and be given an answer set of structures each of which contains the query with the desired stereochemistry. The incorporation of stereochemical information into substructure search should be, for the most part, a straightforward extension of topological search techniques. However, when that information involves relative, as opposed to absolute, stereochemistry, the search problem can be somewhat more... 

In practice, the problem of handling relative configurations in a stereochemical substructure search system may not be relevant to the majority of the searches conducted. Nevertheless, some algorithm for this problem is required if relative stereochemistry is to be handled at all. The algorithm developed in this paper is a viable alternative to the l3rute force approach of generating all the possible stereochemistries imphed by the relative configurations. 

The systems analysis showed that it was important for Dialog to adopt a fully integrated subsystem that would effectively perform structure and substructure searches. Such a subsystem would permit the Dialog program to remain in control of all the communications functions to the user s terminal, but would use searching techniques that were different from those of Dialog and more appropriately suited to the handling of structure information. 

The basic algorithms for structure and substructure search have been applied to the problem of handling generic or... 

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