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Platinum: a database of experimentally measured effects of mutations on structurally defined protein-ligand complexes.

Pires DE, Blundell TL, Ascher DB - Nucleic Acids Res. (2014)

Bottom Line: Drug resistance is a major challenge for the treatment of many diseases and a significant concern throughout the drug development process.The ability to understand and predict the effects of mutations on protein-ligand affinities and their roles in the emergence of resistance would significantly aid treatment and drug design strategies.To minimize differences arising from experimental techniques and to directly compare binding affinities, Platinum considers only changes measured by the same group and with the same amino-acid sequence used for structure determination, providing a direct link between protein structure, how a ligand binds and how mutations alter the affinity of the ligand of the protein.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA, UK dpires@dcc.ufmg.br.

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Platinum entries statistics. In (A), the histogram of the density distribution of the effect of mutations on protein–ligand affinity within Platinum is shown as the fold change (ratio between affinities of reference and mutant). In (B), the histogram of the density distribution of molecular weights of unique ligands in Platinum is shown. The proteins in Platinum are classified by their function, with the proportion of proteins in the most common classes shown in (C). The proteins are also classified phylogenetically in groups and the proportion of data points per class is shown in (D).
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Figure 3: Platinum entries statistics. In (A), the histogram of the density distribution of the effect of mutations on protein–ligand affinity within Platinum is shown as the fold change (ratio between affinities of reference and mutant). In (B), the histogram of the density distribution of molecular weights of unique ligands in Platinum is shown. The proteins in Platinum are classified by their function, with the proportion of proteins in the most common classes shown in (C). The proteins are also classified phylogenetically in groups and the proportion of data points per class is shown in (D).

Mentions: Currently Platinum contains more than 1000 unique data points, with 72% of mutations leading to either a significant increase (16%) or decrease (56%) in protein–ligand affinity of over 2-fold (Figure 3A). Most mutations in Platinum (75%) involve residues directly interacting with the ligand in the three-dimensional structure. Approximately 80% of the data points are from single-point mutations, which are more amenable to computational predictions. The information stored in the database represents a diverse range of proteins, ligands and interactions, as summarized in Table 1. The ligands in the database are quite varied, with molecular weights ranging from 90 to 900 Da (Figure 3B) and including fragments, inhibitors and therapeutics as well as natural co-factors and substrates (other properties of ligands in Platinum are also depicted in Supplementary Figure S2 of Supplementary Material). The proteins present in the database represent a wide range of biological activities (Figure 3C) highlighting the broad range of effects encompassed within Platinum. While the proteins are from a diverse selection of organisms, the majority (60%) are from organisms in the Bacterial Domain and Animalia Kingdom (Figure 3D), with approximately 20% of the data from Homo sapiens proteins. This reflects the research emphasis within these areas.


Platinum: a database of experimentally measured effects of mutations on structurally defined protein-ligand complexes.

Pires DE, Blundell TL, Ascher DB - Nucleic Acids Res. (2014)

Platinum entries statistics. In (A), the histogram of the density distribution of the effect of mutations on protein–ligand affinity within Platinum is shown as the fold change (ratio between affinities of reference and mutant). In (B), the histogram of the density distribution of molecular weights of unique ligands in Platinum is shown. The proteins in Platinum are classified by their function, with the proportion of proteins in the most common classes shown in (C). The proteins are also classified phylogenetically in groups and the proportion of data points per class is shown in (D).
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4384026&req=5

Figure 3: Platinum entries statistics. In (A), the histogram of the density distribution of the effect of mutations on protein–ligand affinity within Platinum is shown as the fold change (ratio between affinities of reference and mutant). In (B), the histogram of the density distribution of molecular weights of unique ligands in Platinum is shown. The proteins in Platinum are classified by their function, with the proportion of proteins in the most common classes shown in (C). The proteins are also classified phylogenetically in groups and the proportion of data points per class is shown in (D).
Mentions: Currently Platinum contains more than 1000 unique data points, with 72% of mutations leading to either a significant increase (16%) or decrease (56%) in protein–ligand affinity of over 2-fold (Figure 3A). Most mutations in Platinum (75%) involve residues directly interacting with the ligand in the three-dimensional structure. Approximately 80% of the data points are from single-point mutations, which are more amenable to computational predictions. The information stored in the database represents a diverse range of proteins, ligands and interactions, as summarized in Table 1. The ligands in the database are quite varied, with molecular weights ranging from 90 to 900 Da (Figure 3B) and including fragments, inhibitors and therapeutics as well as natural co-factors and substrates (other properties of ligands in Platinum are also depicted in Supplementary Figure S2 of Supplementary Material). The proteins present in the database represent a wide range of biological activities (Figure 3C) highlighting the broad range of effects encompassed within Platinum. While the proteins are from a diverse selection of organisms, the majority (60%) are from organisms in the Bacterial Domain and Animalia Kingdom (Figure 3D), with approximately 20% of the data from Homo sapiens proteins. This reflects the research emphasis within these areas.

Bottom Line: Drug resistance is a major challenge for the treatment of many diseases and a significant concern throughout the drug development process.The ability to understand and predict the effects of mutations on protein-ligand affinities and their roles in the emergence of resistance would significantly aid treatment and drug design strategies.To minimize differences arising from experimental techniques and to directly compare binding affinities, Platinum considers only changes measured by the same group and with the same amino-acid sequence used for structure determination, providing a direct link between protein structure, how a ligand binds and how mutations alter the affinity of the ligand of the protein.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA, UK dpires@dcc.ufmg.br.

Show MeSH
Related in: MedlinePlus