PDB ligand database

Additionally, the Maybridge compound library (Version 2003, containing 59194 compounds) is converted into multi-conformational format and screened, analyzing the resulting hit lists for their accordance with the Lipinski drug-likeness criteria as applied to the PDB ligand database. A maximum mol weight of... 

Figure 10.1 Schematic showing the generation of a typical ent in the PDB ligand database.

Figure 10.6 Examples of phenols identified by substructure search ofthe PDB ligand database. The additional calculated parameters can be used to ascertain the nature ofthe local pocket environment and prioritize the examples according to their likely relevance in suggesting bioisosteres.

In the Pfizer in-house IC50 data set, there are 1059 pairs of compounds consisting of a carboxylic add and the equivalent tetrazole that have been tested in the same assay. In order to define a binding environment for the acid/tetrazole, an attempt was made to map each pair to its most relevant pocket in the PDB ligand database by identifying the most similar cocrystallized ligand in a protein from the same family. 

A simple substructure search of the PDB ligand SMILES database yielded all examples of phenols. Three such examples are illustrated in Figure 10.6. Each of these was clearly involved in a different type of environment, information that was captured in the descriptors automatically output by the search. If a replacement were being sought for a phenol in a buried environment, for example, an aminergic GPCR,... 

Cambridge Structural Database De Novo Ligand Design Pharmacophore and Drug Discovery Protein Data Bank (PDB) A Database of 3D Structural Information of Biological Macromolecules Structure Databases Three-dimensional Structure Generation Automation Three-dimensional Structure Searching. 

A number of structured databases have been developed to classify proteins according to the three-dimensional structures. Many of these are accessible via the World Wide Web, T1 protein databanlc (PDB [Bernstein d al. 1977]) is the primary source of data about the stru tures of biological macromolecules and contains a large number of structures, but many i these are of identical proteins (complexed with different ligands or determined at differet resolutions) or are of close homologues. 

Fig. 8. The EF hand represents a widespread Ca2+ binding motif that was first characterized in calmodulin. Generally, EF hands are observed in pairs. Each consists of two short stretches of o-helix connected by a loop. Two possible sets of ligands have been identified through which calcium cations bind to the residues comprising the loop (see text). This figure illustrates the structural forms observed that relate to different Ca2+ binding states (PDB closed, 1GFC open, 1GLL semi-open, 1WDC). Figure from http //structbio.vanderbilt.edu.chazin/cabp database/seq.

Figure 7.8. The substrate interaction at the active site of an enzyme. The interaction of tetra-A/,A/,A/,A/-acetylchitotetraose (NAG4) with amino acid residues at the active site of lysozyme (ILZC.pdb) can be viewed/saved at PDBsum server (Enyme Structure Database->PDBsum->LIGPLOT of interactions under Ligand) linked to the Enzyme Structure Database.

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