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SuperLigands - a database of ligand structures derived from the Protein Data Bank.

Michalsky E, Dunkel M, Goede A, Preissner R - BMC Bioinformatics (2005)

Bottom Line: Structural similarity of the compounds can be detected by calculation of Tanimoto coefficients and by three-dimensional superposition.SuperLigands supplements the set of existing resources of information about small molecules bound to PDB structures.Allowing for three-dimensional comparison of the compounds as a novel feature, this database represents a valuable means of analysis and prediction in the field of biological and medical research.

View Article: PubMed Central - HTML - PubMed

Affiliation: BCB (Berlin Center for Genome Based Bioinformatics) at Institute of Biochemistry, Charité (University Medicine Berlin), Monbijoustr, 2, 10117 Berlin, Germany. elke.michalsky@charite.de

ABSTRACT

Background: Currently, the PDB contains approximately 29,000 protein structures comprising over 70,000 experimentally determined three-dimensional structures of over 5,000 different low molecular weight compounds. Information about these PDB ligands can be very helpful in the field of molecular modelling and prediction, particularly for the prediction of protein binding sites and function.

Description: Here we present an Internet accessible database delivering PDB ligands in the MDL Mol file format which, in contrast to the PDB format, includes information about bond types. Structural similarity of the compounds can be detected by calculation of Tanimoto coefficients and by three-dimensional superposition. Topological similarity of PDB ligands to known drugs can be assessed via Tanimoto coefficients.

Conclusion: SuperLigands supplements the set of existing resources of information about small molecules bound to PDB structures. Allowing for three-dimensional comparison of the compounds as a novel feature, this database represents a valuable means of analysis and prediction in the field of biological and medical research.

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Related in: MedlinePlus

Usage of the web interface of SuperLigands. From the main menu, the form Compound search can be reached. Here, a PDB ligand can be searched after hetero-ID, name, molecular formula or PDB identifier. In the first column of the results table, two buttons can be found to retrieve more information. The FULL info button delivers detailed information about the selected PDB ligand like molecular formula, atom numbers and occurrence in the PDB. After clicking the DRUGS button, a two-dimensional similarity search among the drugs in the SuperDrug database [16] is performed. The best hits are displayed in a new window. From here, they can be spatially superposed. In the figure, this procedure was carried out for celecoxib, a COX-2 inhibitor which was recently categorised as problematic (see the "Pfizer Statement on New Information Regarding Cardiovascular Safety of Celebrex" [18]). The two-dimensional similarity search in the SuperDrug database delivers only hits below 72% Tanimoto similarity. A following spatial superposition of the best hits reveals a further COX-2 inhibitor, namely valdecoxib, (RMSD 0.26Å and 21 of 22 atoms superposed) as very similar to celecoxib. The Tanimoto similarity of celecoxib and valdecoxib is only 65% and there are two drugs more similar to celecoxib: Sulfaphenazole (71% Tanimoto similarity, spatial superposition with 0.65Å RMSD and 15 of 22 atoms superposed) and Sulfamazone (67% Tanimoto similarity, spatial superposition with 0.32Å RMSD and 17 of 26 atoms superposed). Nevertheless, the three-dimensional comparison here proves to be very important to reveal molecular similarities in addition to topological comparison (as also shown in the example in the section Utility), which is confirmed by the fact that valdecoxib was categorised as toxic [19] and sales of this drug were suspended recently [20].
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Figure 1: Usage of the web interface of SuperLigands. From the main menu, the form Compound search can be reached. Here, a PDB ligand can be searched after hetero-ID, name, molecular formula or PDB identifier. In the first column of the results table, two buttons can be found to retrieve more information. The FULL info button delivers detailed information about the selected PDB ligand like molecular formula, atom numbers and occurrence in the PDB. After clicking the DRUGS button, a two-dimensional similarity search among the drugs in the SuperDrug database [16] is performed. The best hits are displayed in a new window. From here, they can be spatially superposed. In the figure, this procedure was carried out for celecoxib, a COX-2 inhibitor which was recently categorised as problematic (see the "Pfizer Statement on New Information Regarding Cardiovascular Safety of Celebrex" [18]). The two-dimensional similarity search in the SuperDrug database delivers only hits below 72% Tanimoto similarity. A following spatial superposition of the best hits reveals a further COX-2 inhibitor, namely valdecoxib, (RMSD 0.26Å and 21 of 22 atoms superposed) as very similar to celecoxib. The Tanimoto similarity of celecoxib and valdecoxib is only 65% and there are two drugs more similar to celecoxib: Sulfaphenazole (71% Tanimoto similarity, spatial superposition with 0.65Å RMSD and 15 of 22 atoms superposed) and Sulfamazone (67% Tanimoto similarity, spatial superposition with 0.32Å RMSD and 17 of 26 atoms superposed). Nevertheless, the three-dimensional comparison here proves to be very important to reveal molecular similarities in addition to topological comparison (as also shown in the example in the section Utility), which is confirmed by the fact that valdecoxib was categorised as toxic [19] and sales of this drug were suspended recently [20].

Mentions: As an additional feature of SuperLigands, similarity of PDB ligands to known drugs can be assessed in a comfortable manner. Starting with a ligand, a two-dimensional similarity search as described above can be initiated, not only among the PDB ligands but also in a database containing the structures of known drugs (SuperDrug Database [16], [32]). The drug structures found can be superposed spatially (for an example, see Figure 1).


SuperLigands - a database of ligand structures derived from the Protein Data Bank.

Michalsky E, Dunkel M, Goede A, Preissner R - BMC Bioinformatics (2005)

Usage of the web interface of SuperLigands. From the main menu, the form Compound search can be reached. Here, a PDB ligand can be searched after hetero-ID, name, molecular formula or PDB identifier. In the first column of the results table, two buttons can be found to retrieve more information. The FULL info button delivers detailed information about the selected PDB ligand like molecular formula, atom numbers and occurrence in the PDB. After clicking the DRUGS button, a two-dimensional similarity search among the drugs in the SuperDrug database [16] is performed. The best hits are displayed in a new window. From here, they can be spatially superposed. In the figure, this procedure was carried out for celecoxib, a COX-2 inhibitor which was recently categorised as problematic (see the "Pfizer Statement on New Information Regarding Cardiovascular Safety of Celebrex" [18]). The two-dimensional similarity search in the SuperDrug database delivers only hits below 72% Tanimoto similarity. A following spatial superposition of the best hits reveals a further COX-2 inhibitor, namely valdecoxib, (RMSD 0.26Å and 21 of 22 atoms superposed) as very similar to celecoxib. The Tanimoto similarity of celecoxib and valdecoxib is only 65% and there are two drugs more similar to celecoxib: Sulfaphenazole (71% Tanimoto similarity, spatial superposition with 0.65Å RMSD and 15 of 22 atoms superposed) and Sulfamazone (67% Tanimoto similarity, spatial superposition with 0.32Å RMSD and 17 of 26 atoms superposed). Nevertheless, the three-dimensional comparison here proves to be very important to reveal molecular similarities in addition to topological comparison (as also shown in the example in the section Utility), which is confirmed by the fact that valdecoxib was categorised as toxic [19] and sales of this drug were suspended recently [20].
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC1173082&req=5

Figure 1: Usage of the web interface of SuperLigands. From the main menu, the form Compound search can be reached. Here, a PDB ligand can be searched after hetero-ID, name, molecular formula or PDB identifier. In the first column of the results table, two buttons can be found to retrieve more information. The FULL info button delivers detailed information about the selected PDB ligand like molecular formula, atom numbers and occurrence in the PDB. After clicking the DRUGS button, a two-dimensional similarity search among the drugs in the SuperDrug database [16] is performed. The best hits are displayed in a new window. From here, they can be spatially superposed. In the figure, this procedure was carried out for celecoxib, a COX-2 inhibitor which was recently categorised as problematic (see the "Pfizer Statement on New Information Regarding Cardiovascular Safety of Celebrex" [18]). The two-dimensional similarity search in the SuperDrug database delivers only hits below 72% Tanimoto similarity. A following spatial superposition of the best hits reveals a further COX-2 inhibitor, namely valdecoxib, (RMSD 0.26Å and 21 of 22 atoms superposed) as very similar to celecoxib. The Tanimoto similarity of celecoxib and valdecoxib is only 65% and there are two drugs more similar to celecoxib: Sulfaphenazole (71% Tanimoto similarity, spatial superposition with 0.65Å RMSD and 15 of 22 atoms superposed) and Sulfamazone (67% Tanimoto similarity, spatial superposition with 0.32Å RMSD and 17 of 26 atoms superposed). Nevertheless, the three-dimensional comparison here proves to be very important to reveal molecular similarities in addition to topological comparison (as also shown in the example in the section Utility), which is confirmed by the fact that valdecoxib was categorised as toxic [19] and sales of this drug were suspended recently [20].
Mentions: As an additional feature of SuperLigands, similarity of PDB ligands to known drugs can be assessed in a comfortable manner. Starting with a ligand, a two-dimensional similarity search as described above can be initiated, not only among the PDB ligands but also in a database containing the structures of known drugs (SuperDrug Database [16], [32]). The drug structures found can be superposed spatially (for an example, see Figure 1).

Bottom Line: Structural similarity of the compounds can be detected by calculation of Tanimoto coefficients and by three-dimensional superposition.SuperLigands supplements the set of existing resources of information about small molecules bound to PDB structures.Allowing for three-dimensional comparison of the compounds as a novel feature, this database represents a valuable means of analysis and prediction in the field of biological and medical research.

View Article: PubMed Central - HTML - PubMed

Affiliation: BCB (Berlin Center for Genome Based Bioinformatics) at Institute of Biochemistry, Charité (University Medicine Berlin), Monbijoustr, 2, 10117 Berlin, Germany. elke.michalsky@charite.de

ABSTRACT

Background: Currently, the PDB contains approximately 29,000 protein structures comprising over 70,000 experimentally determined three-dimensional structures of over 5,000 different low molecular weight compounds. Information about these PDB ligands can be very helpful in the field of molecular modelling and prediction, particularly for the prediction of protein binding sites and function.

Description: Here we present an Internet accessible database delivering PDB ligands in the MDL Mol file format which, in contrast to the PDB format, includes information about bond types. Structural similarity of the compounds can be detected by calculation of Tanimoto coefficients and by three-dimensional superposition. Topological similarity of PDB ligands to known drugs can be assessed via Tanimoto coefficients.

Conclusion: SuperLigands supplements the set of existing resources of information about small molecules bound to PDB structures. Allowing for three-dimensional comparison of the compounds as a novel feature, this database represents a valuable means of analysis and prediction in the field of biological and medical research.

Show MeSH
Related in: MedlinePlus