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Creation of a free, Internet-accessible database: the Multiple Target Ligand Database.

Chen C, He Y, Wu J, Zhou J - J Cheminform (2015)

Bottom Line: The entire database is free for online searching, browsing, and downloading.As a crucial expansion of the PDB, increasing numbers of MTLs will be included in the MTLD.Eventually, it will become an efficient platform to obtain useful information on MTLs and their underlying polypharmacology.

View Article: PubMed Central - PubMed

Affiliation: North China Institute of Science and Technology, Beijing, China.

ABSTRACT

Background: Polypharmacology plays an important part in drug discovery, and remains a major challenge in drug development. Identification of the underlying polypharmacology of a drug, as well as development of polypharmacological drugs, have become important issues in the pharmaceutical industry and academia.

Description: Herein, through data mining of the Protein Data Bank (PDB), a free, Internet-accessible database called the Multiple Target Ligand Database (MTLD; www.mtdcadd.com) was constructed. The MTLD contains 1,732 multiple-target ligands (MTLs) which bind to 14,996 binding sites extracted from 12,759 PDB structures. Among MTLs, 222 entries are approved drugs and 1,334 entries are drug-like compounds. The MTLD could be an extremely useful tool in the development of polypharmacological drugs. It also sheds light on the side effects of drugs through anticipation of their multiple functions and similarities in the binding sites of multiple targets. The entire database is free for online searching, browsing, and downloading.

Conclusion: As a crucial expansion of the PDB, increasing numbers of MTLs will be included in the MTLD. Eventually, it will become an efficient platform to obtain useful information on MTLs and their underlying polypharmacology.

No MeSH data available.


Related in: MedlinePlus

Statistical analyses for entries in the MTLD. (A) 815 (47.1%) entries belong to the Kyoto Encyclopedia of Genes and Genomes database; (B) 222 (12.8%) entries are approved drugs from the DrugBank database; (C) 1334 (76.9%) entries are drug-like compounds according to Lipinski’s rule of five; (D) molecular weights of most ligands are ≤500 Da. (E) Statistical analyses of the target number of ligands included in the MTLD: 795 ligand entries bind two targets; 551 ligand entries bind 3–5 targets; 189 ligand entries bind 6–10 targets; and 197 ligand entries bind to >10 targets; (F) Comparison of the conformation of a ligand bound to different targets. Root-mean-square deviation (RMSD) value was calculated to evaluate the change in conformation: the RMSD value of most ligands was ≤2 Å, indicating a small conformational change.
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Fig2: Statistical analyses for entries in the MTLD. (A) 815 (47.1%) entries belong to the Kyoto Encyclopedia of Genes and Genomes database; (B) 222 (12.8%) entries are approved drugs from the DrugBank database; (C) 1334 (76.9%) entries are drug-like compounds according to Lipinski’s rule of five; (D) molecular weights of most ligands are ≤500 Da. (E) Statistical analyses of the target number of ligands included in the MTLD: 795 ligand entries bind two targets; 551 ligand entries bind 3–5 targets; 189 ligand entries bind 6–10 targets; and 197 ligand entries bind to >10 targets; (F) Comparison of the conformation of a ligand bound to different targets. Root-mean-square deviation (RMSD) value was calculated to evaluate the change in conformation: the RMSD value of most ligands was ≤2 Å, indicating a small conformational change.

Mentions: To better understand constitution of the MTLs in the MTLD, statistical analyses of the MTLD were undertaken (Figure 2). First, the KEGG database (a database of small molecules, biopolymers, and other chemical substances relevant to biological systems) was used to analyse the relationship between MTLD entries and biological processes. In total, 815 MTL entries in the MTLD also belonged to the KEGG database (≈47.1% of overall entries; Figure 2A), which includes various amino acids, saccharides, nucleotides, and lipids. Similarly, in contrast to the known drugs listed in the DrugBank, 222 approved drugs were found in the MTLD (≈12.8% of overall entries; Figure 2B). In particular, by using the module “QuaSAR-Descriptor” included in Molecular Operating Environment (Chemical Computing Group, Montreal, Canada) according to Lipinski's rule of five, 1,334 entries were predicted to be drug-like compounds (≈76.9% of overall entries; Figure 2C). Analyses of the distribution of the molecular weights of MTLs in the MTLD indicated that most of the MTLs had molecular weights <500 Da, and that a very small portion of MTLs had a molecular weight >1000 Da (Figure 2D). Thus, statistical analyses suggested that the MTLD could be highly relevant to biological processes and the action mechanism of drugs.Figure 2


Creation of a free, Internet-accessible database: the Multiple Target Ligand Database.

Chen C, He Y, Wu J, Zhou J - J Cheminform (2015)

Statistical analyses for entries in the MTLD. (A) 815 (47.1%) entries belong to the Kyoto Encyclopedia of Genes and Genomes database; (B) 222 (12.8%) entries are approved drugs from the DrugBank database; (C) 1334 (76.9%) entries are drug-like compounds according to Lipinski’s rule of five; (D) molecular weights of most ligands are ≤500 Da. (E) Statistical analyses of the target number of ligands included in the MTLD: 795 ligand entries bind two targets; 551 ligand entries bind 3–5 targets; 189 ligand entries bind 6–10 targets; and 197 ligand entries bind to >10 targets; (F) Comparison of the conformation of a ligand bound to different targets. Root-mean-square deviation (RMSD) value was calculated to evaluate the change in conformation: the RMSD value of most ligands was ≤2 Å, indicating a small conformational change.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4403778&req=5

Fig2: Statistical analyses for entries in the MTLD. (A) 815 (47.1%) entries belong to the Kyoto Encyclopedia of Genes and Genomes database; (B) 222 (12.8%) entries are approved drugs from the DrugBank database; (C) 1334 (76.9%) entries are drug-like compounds according to Lipinski’s rule of five; (D) molecular weights of most ligands are ≤500 Da. (E) Statistical analyses of the target number of ligands included in the MTLD: 795 ligand entries bind two targets; 551 ligand entries bind 3–5 targets; 189 ligand entries bind 6–10 targets; and 197 ligand entries bind to >10 targets; (F) Comparison of the conformation of a ligand bound to different targets. Root-mean-square deviation (RMSD) value was calculated to evaluate the change in conformation: the RMSD value of most ligands was ≤2 Å, indicating a small conformational change.
Mentions: To better understand constitution of the MTLs in the MTLD, statistical analyses of the MTLD were undertaken (Figure 2). First, the KEGG database (a database of small molecules, biopolymers, and other chemical substances relevant to biological systems) was used to analyse the relationship between MTLD entries and biological processes. In total, 815 MTL entries in the MTLD also belonged to the KEGG database (≈47.1% of overall entries; Figure 2A), which includes various amino acids, saccharides, nucleotides, and lipids. Similarly, in contrast to the known drugs listed in the DrugBank, 222 approved drugs were found in the MTLD (≈12.8% of overall entries; Figure 2B). In particular, by using the module “QuaSAR-Descriptor” included in Molecular Operating Environment (Chemical Computing Group, Montreal, Canada) according to Lipinski's rule of five, 1,334 entries were predicted to be drug-like compounds (≈76.9% of overall entries; Figure 2C). Analyses of the distribution of the molecular weights of MTLs in the MTLD indicated that most of the MTLs had molecular weights <500 Da, and that a very small portion of MTLs had a molecular weight >1000 Da (Figure 2D). Thus, statistical analyses suggested that the MTLD could be highly relevant to biological processes and the action mechanism of drugs.Figure 2

Bottom Line: The entire database is free for online searching, browsing, and downloading.As a crucial expansion of the PDB, increasing numbers of MTLs will be included in the MTLD.Eventually, it will become an efficient platform to obtain useful information on MTLs and their underlying polypharmacology.

View Article: PubMed Central - PubMed

Affiliation: North China Institute of Science and Technology, Beijing, China.

ABSTRACT

Background: Polypharmacology plays an important part in drug discovery, and remains a major challenge in drug development. Identification of the underlying polypharmacology of a drug, as well as development of polypharmacological drugs, have become important issues in the pharmaceutical industry and academia.

Description: Herein, through data mining of the Protein Data Bank (PDB), a free, Internet-accessible database called the Multiple Target Ligand Database (MTLD; www.mtdcadd.com) was constructed. The MTLD contains 1,732 multiple-target ligands (MTLs) which bind to 14,996 binding sites extracted from 12,759 PDB structures. Among MTLs, 222 entries are approved drugs and 1,334 entries are drug-like compounds. The MTLD could be an extremely useful tool in the development of polypharmacological drugs. It also sheds light on the side effects of drugs through anticipation of their multiple functions and similarities in the binding sites of multiple targets. The entire database is free for online searching, browsing, and downloading.

Conclusion: As a crucial expansion of the PDB, increasing numbers of MTLs will be included in the MTLD. Eventually, it will become an efficient platform to obtain useful information on MTLs and their underlying polypharmacology.

No MeSH data available.


Related in: MedlinePlus