Search query

The next example shows how different search queries can be combined to shed more light onto a series of related reactions. A reaction substructure search for reactions that break a P-O bond provided 304 reactions as hits. Figure 10.3-27 shows one of the reactions in this hit list. 

Figure 10.3-54. Derivation of a reaction substructure search query. The a" for atom 1 and 8 indicates that these atoms have to be aromatic in the found reactions.

This method represents the most common and traditional application of computational tools to rational drug design. From a list of molecules of known activity, one can establish a 3D-pharmacophore hypothesis that is then transformed into a 3D-search query. This query is then used to search a 3D database for structures that fit the hypothesis within a certain tolerance. If the yield of active molecules is significant, then the query can be used to predict activities on novel compounds. In our situation, the enantiophore is built from the superposition of a list of sample molecules, which are all well separated on a given CSR Hence, the common features of this series of molecules can become a good enantiophore hypothesis for the enantiores-olution on this CSR... 

In Fig. 4-11, two different samples are displayed in their original conformations and conformations fitted to the query as they are highlighted by the CFS search process. The CFS process rotates single bonds between two atoms to find the maximum and minimum difference possible with the distance and angle constraints. Then, using a torsional fitter, it attempts to minimize in those conformations the deviations between measured values of 3D constraints and the values that are specified in the 3D-search query. 

These first-created enantiophores are rudimentary, but may serve as useful guidelines for a further design of more sophisticated and efficient search queries in consideration of possible alternative modes of binding and conformational changes in the CSP receptor structure. Undoubtedly, this query optimization will soon take advantage of the backgrounds of our new 3D-database project called CHIR-SOURCE. 

The CrossFire Beilstein database is the world s largest compilation of chemical facts. This database indexes three primary data domains substances, reactions and literature. The substance domain stores structural information with aU associated facts and literature references, including chemical, physical and bioactivity data. The reaction domain details the preparation of substances, enabling scientists to investigate specific reaction pathways with reaction search queries. The literature domain includes citations, titles and abstracts, which are hyperhnked to the substance and reaction domain entries. It contains over 320 million experimental data, over 10 million reactions and data indexed from over 175 journals. 

Fragment search in the Cambridge Crystallographic Data Base reveals 127 hits out of 42381 entries (state May 1985) having dimethyl sulfoxide as the search query and allowing for the presence of metal atoms. In absence of such elements, the number of hits is reduced to 27. 

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. 

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

Many chemists have been surprized to discover that their reagent database applications have not proved adequate for Combinatorial Chemistry. In some instances, the required search queries can not be answered. For example, list the 10 most similar reagents to a given... 

The results are presented in terms of bibliographic and chemical text, 2D chemical diagrams, 3D structure diagrams at the molecular or extended crystal structure levels, and also as tables of geometrical parameters for each located substructure or chemical fragment. The search query is via... 

The binding models were vahdated according to their coverage (capacity as a three-dimensional (3D) database search queries) and predictive... 

Some hits also revealed sufficient selectivity of type 1 inhibition versus the type 2 isoform, which is advantageous for the side-effect profile of these compounds. Comparison of the model for llp-HSDl inhibitors with the X-ray crystal structure (which was published shortly after model generation and VS) showed good correlation of the chemical features responsible for ligand binding. In another study, a combination of common feature-based qualitative and quantitative models was used as 3D pharmacophore search query to successfully detect novel endothelin-A antagonistic lead structures. 

Figure 7 Yearly number of publications in the CJACS file mentioning three other molecular modeling programs. CDL is Chemical Design Ltd. The search queries for the curves were (1) macromodel, (2) pcmodel or serena, (3) chemx or chem(w)x or chemical(w)design(w)ltd or chemical(w)design(w)limited, (4) serena, and (5) chemi-cal(w)design(w)ltd or chemical(w)design(w)limited.

Figure 9 Yearly number of publications in the CJACS file related to MM2, MM3, or MMX. The search queries for each curve were (1) mm2 and (force(w)field or molecular(w)mechanics), (2) (mm2 or mm3) and allinger, (3) mm3 and (force(w)field or molecular(w)mechanics), (4) (mmx or mm(w)x) and (force(w)field or molecular(w)mechanics), and (5) (mm2 or mm3) and (technical(w)utilization or tripos or molecular(w)design).

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