Proteins Substructure Searching

Key words Protein kinase, kinase-targeted library, library design, kinase chemical cores, substructure search, SMARTS Query, subsetting, binding mode annotation. 

Koch et al. [111] have discussed the use of graph theoretical techniques in an attempt to find rules to relate beta sheet topology to amino acid sequence and for the comparison of beta sheet structures. They defined a graph representation for every protein in the PDB that contains beta sheets, notations and graphic representations for sheets which described the sequential and topological neighbourhoods of the strands, and constructed tools for substructure searches of this database. 

Before addressing some aspects of, broadly speaking, ligand-receptor interactions, a critical evaluation of protein structure determination was felt in order. This is then followed by accounts of docking and scoring, pharmacophore identification 3D searching, substructure searching, and molecular descriptors. 

In conclusion, we note that most studies to date have considered only small molecules with contributions to the field being principally from medicinal chemists and information scientists. However, recent papers on substructure searching in macromolecules indicate that protein crystallographers and molecular biologists " are now also getting involved. We believe that the interactions between the disparate disciplines will prove fruitful in the further development of techniques for three-dimensional substructure searching of both small and large molecules. 

E. M. Mitchell, P. Willett, P. j. Artymiuk, and D. W. Rice, Three-Dimensional Substructure Searching in the Protein Data Bank. British Library, London, 1988. 

In the example, given substructural searches are apphed to remove groups that generally react with biological molecules like proteins or nucleic acids. 

Grindley, H.M. 3-D Distance Comparisons in Protein Secondary Structure Motifs For Substructure Search Refinement . M.Sc. dissertation. University of Sheffield, 1988. 

Inorganic Three-dimensional Structure Databases Molecular Docking and Structure-based Design Protein Data Bank (PDB) A Database of 3D Structural Information of Biological Macromolecules Structural Similarity Measures for Database Searching Structure and Substructure Searching Structure Databases Structure Representation Three-dimensional Structure Searching,... 

Template recognition is the process of finding the most similar sequence. The researcher must choose how to compute similarity. It is possible to run a fast, approximate search of many sequences or a slow, accurate search of a few sequences. Sequences that should be analyzed more carefully are the same protein from a different species, proteins with a similar function or from the same metabolic pathway, or a library of commonly observed substructures if available. 

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