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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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Statistics: comparison of PDB ligands with drugs. Chemical properties of 5040 PDB ligands and 2396 drug molecules are compared: histograms for numbers of hydrogen bond donors and acceptors, logP value and molecular weight are shown. Molecular weight within [100,200) means that the molecular weight is greater than or equal to 100 and less than 200. Those areas for which the Lipinski "Rule of 5" is fulfilled, are highlighted in grey.
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Figure 2: Statistics: comparison of PDB ligands with drugs. Chemical properties of 5040 PDB ligands and 2396 drug molecules are compared: histograms for numbers of hydrogen bond donors and acceptors, logP value and molecular weight are shown. Molecular weight within [100,200) means that the molecular weight is greater than or equal to 100 and less than 200. Those areas for which the Lipinski "Rule of 5" is fulfilled, are highlighted in grey.

Mentions: Furthermore, some chemical properties of PDB ligands and drugs have been compared (see Figure 2). The distributions of numbers of hydrogen bond donors for PDB ligands and drugs differ most significantly. A bigger percentage of the drugs (26%) have no hydrogen bond donor, the largest fraction of the PDB ligands (19%) have two of them. About half of the drugs have no or only one hydrogen bond donor, which applies for only a quarter of the PDB ligands. About one third of the drugs have three or four hydrogen bond acceptors, the fractions of drugs with nine or more hydrogen bond acceptors drop below 3%. For the PDB ligands, the distribution is more flat: only 22% of them have three or four hydrogen bond acceptors, still over 3% of them have 11 hydrogen bond acceptors. Most drugs have a logP value around 3, and the logP values of the PDB ligands accumulate around the negative value -1. Approximately the same fraction of PDB ligands and drugs are "drug-like" according to the Lipinski "Rule of five" [17]: 92 and 91%, respectively, have a logP value less than 5, although altogether the logP values of the drugs are closer to this critical value. A majority of the PDB ligands have very low molecular weights in comparison to the drugs, which supposedly is be caused by the fact that in proteins often very small solvent molecules are bound. Nevertheless, slightly more (5%) drugs than PDB ligands fulfil the Lipinski "Rule of five" regarding the molecular weight. The same applies for the numbers of hydrogen bond donors (and acceptors): 7% (5%) more drugs fulfil the Lipinski "Rule of five".


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

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

Statistics: comparison of PDB ligands with drugs. Chemical properties of 5040 PDB ligands and 2396 drug molecules are compared: histograms for numbers of hydrogen bond donors and acceptors, logP value and molecular weight are shown. Molecular weight within [100,200) means that the molecular weight is greater than or equal to 100 and less than 200. Those areas for which the Lipinski "Rule of 5" is fulfilled, are highlighted in grey.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC1173082&req=5

Figure 2: Statistics: comparison of PDB ligands with drugs. Chemical properties of 5040 PDB ligands and 2396 drug molecules are compared: histograms for numbers of hydrogen bond donors and acceptors, logP value and molecular weight are shown. Molecular weight within [100,200) means that the molecular weight is greater than or equal to 100 and less than 200. Those areas for which the Lipinski "Rule of 5" is fulfilled, are highlighted in grey.
Mentions: Furthermore, some chemical properties of PDB ligands and drugs have been compared (see Figure 2). The distributions of numbers of hydrogen bond donors for PDB ligands and drugs differ most significantly. A bigger percentage of the drugs (26%) have no hydrogen bond donor, the largest fraction of the PDB ligands (19%) have two of them. About half of the drugs have no or only one hydrogen bond donor, which applies for only a quarter of the PDB ligands. About one third of the drugs have three or four hydrogen bond acceptors, the fractions of drugs with nine or more hydrogen bond acceptors drop below 3%. For the PDB ligands, the distribution is more flat: only 22% of them have three or four hydrogen bond acceptors, still over 3% of them have 11 hydrogen bond acceptors. Most drugs have a logP value around 3, and the logP values of the PDB ligands accumulate around the negative value -1. Approximately the same fraction of PDB ligands and drugs are "drug-like" according to the Lipinski "Rule of five" [17]: 92 and 91%, respectively, have a logP value less than 5, although altogether the logP values of the drugs are closer to this critical value. A majority of the PDB ligands have very low molecular weights in comparison to the drugs, which supposedly is be caused by the fact that in proteins often very small solvent molecules are bound. Nevertheless, slightly more (5%) drugs than PDB ligands fulfil the Lipinski "Rule of five" regarding the molecular weight. The same applies for the numbers of hydrogen bond donors (and acceptors): 7% (5%) more drugs fulfil the Lipinski "Rule of five".

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