Three database searching

It is also possible to extend this concept to cover the presence of more than one distinct segm pair in a pair of sequences (for example, if there are three MSPs present with scores of 40, and 50 then one can calculate the probabOity of finding three pairs with at least a score of by chance). The ability of BLAST to provide a quantitative significance of any match fou is a particularly useful feature of the program, which, with its continuing development a availability, has made it the most widely used method for sequence database searching. 

Good A C and J S Mason 1995. Three-Dimensional Structure Database Searches. In Lipkowitz K B and D B Boyd (Editors) Reviews in Computational Chemistry Volume 7. New York, VCH Publishers, pp. 67-117. 

DP Mamott, IG Dougall, P Meghani, Y-J Liu, DR Flower. Lead generation using pharmacophore mapping and three-dimensional database searching Application to muscarinic M3 receptor antagonists. J Med Chem 42 3210-3216, 1999. 

Varady J, Wu X, Fang X, Min J, Hu Z, Levant B, Wang S. Molecular modeling of the three-dimensional structure of dopamine 3 (D3) subtype receptor discovery of novel and potent D3 ligands through a hybrid pharmacophore-and structure-based database searching approach. / Med Chem 2003 46 4377-92. 

Kurogi Y, Miyata K, Okamura T, Hashimoto K, Tsutsumi K, Nasu M, Moriyasu M. Discovery of novel mesangial cell proliferation inhibitors using a three-dimensional database searching method. J Med Chem 2001 44 2304-7. 

Andrew C. Good and Jonathan S. Mason, Three-Dimensional Structure Database Searches. 

Studying the sequences of farnesylated proteins indicated that all lipidated proteins bear a cysteine residue near the C-terminus revealing the CAAX-motif, where C is a cysteine, A stands for an aliphatic amino acid, and X can be any amino acid. Database searches resulted in more prenylated proteins, all bearing the CAAX-motif, in systems from lower eukaryotes to mammals. A closer look at the mature proteins revealed that prenylation was only the first step of processing of the CAAX-motif-encoded proteins. After transfer of the isoprene unit, the last three amino acids are cleaved proteolytically by an endoprotease and the C-terminal cysteine is carboxymethylated by a methyltransferase. ... 

SPLICE - a program to assemble partial query solutions from three-dimensional database searches into novel ligands. 

Good, A.C. and M.ason, ).S. Three-dimensional stmcture database searches. Reviews in Computational Chemistry. Wiley, New York, 1996, 67-117. 

Kurogi, Y. and Guner, O.F. Pharmacophore modeling and three-dimensional database searching for dmg design using catalyst. Curr. 

Kaminski, J.J., Rane, D.F., Snow, M.E., Weber, L, and Rothofsky, M.L Identification of novel farnesyl protein transferase inhibitors using three-dimensional database searching methods./. Med. Chem. 1997, 40, 4103-4112. 

Greenidge, P.A., Carlsson, B., Biadh, L.G., and Gillner, M. Pharmacophores incorporating numerous excluded volumes defined by x-ray crystallographic structure in three-dimensional database searching application to the thyroid hormone receptor./. Med. Chem. 1998, 41, 2503-2512. 

Alternatively, Giiner and Henry (14) have introduced the G-H score, which is a weighted average of recall and precision. The score was originally developed for evaluating the effectiveness of three-dimensional (3D) database searches but can be applied to the evaluation of any sort of search for which qualitative bioactivity data are available. Using the previous notation, the G-H score is defined to be... 

The USR (Ultrafast Shape Recognition) Method. This method was reported by Ballester and Richards (53) for compound database search on the basis of molecular shape similarity. It was reportedly capable of screening billions of compounds for similar shapes on a single computer. The method is based on the notion that the relative position of the atoms in a molecule is completely determined by inter-atomic distances. Instead of using all inter-atomic distances, USR uses a subset of distances, reducing the computational costs. Specifically, the distances between all atoms of a molecule to each of four strategic points are calculated. Each set of distances forms a distribution, and the three moments (mean, variance, and skewness) of the four distributions are calculated. Thus, for each molecule, 12 USR descriptors are calculated. The inverse of the translated and scaled Manhattan distance between two shape descriptors is used to measure the similarity between the two molecules. A value of 1 corresponds to maximum similarity and a value of 0 corresponds to minimum similarity. 

Another issue that should be addressed briefly is the relationship between size and resolution of a conformational model particularly in terms of coverage of the low-energy regions of the accessible conformational space. The coverage should at any rate be consistent with the precision of the application which uses the conformational model. During three-dimensional pharmacophore generation for database search purposes, the restriction is given by the tolerance of the pharmacophore query. It has been shown in principle that a limited number of... 

The database search process starts with a rapid screening process within which molecules possessing properties required from potential hits are sorted out from those that can be excluded a priori. The screen involves substructure match followed by screens matching three-dimensional pharmacophore features, molecular shapes or exclusion volumes and text constraints (ID properties) if present in the query (through Oracle). All this greatly reduces the number of potential hit compounds in the database. The next step of the search pro-... 

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