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Investigation of atomic level patterns in protein--small ligand interactions.

Chen K, Kurgan L - PLoS ONE (2009)

Bottom Line: Similar patterns were found for the coordination bonds.We show that for a given type (group) of ligands and type of the interaction force, majority of protein-ligand interactions are repetitive and could be summarized with several simple atomic-level patterns.We summarize and analyze 10 frequently occurring interaction patterns that cover 56% of all considered complexes and we show a practical application for the patterns that concerns interactions with organic compounds.

View Article: PubMed Central - PubMed

Affiliation: Department of Electrical and Computer Engineering, University of Alberta, Edmonton, Alberta, Canada.

ABSTRACT

Background: Shape complementarity and non-covalent interactions are believed to drive protein-ligand interaction. To date protein-protein, protein-DNA, and protein-RNA interactions were systematically investigated, which is in contrast to interactions with small ligands. We investigate the role of covalent and non-covalent bonds in protein-small ligand interactions using a comprehensive dataset of 2,320 complexes.

Methodology and principal findings: We show that protein-ligand interactions are governed by different forces for different ligand types, i.e., protein-organic compound interactions are governed by hydrogen bonds, van der Waals contacts, and covalent bonds; protein-metal ion interactions are dominated by electrostatic force and coordination bonds; protein-anion interactions are established with electrostatic force, hydrogen bonds, and van der Waals contacts; and protein-inorganic cluster interactions are driven by coordination bonds. We extracted several frequently occurring atomic-level patterns concerning these interactions. For instance, 73% of investigated covalent bonds were summarized with just three patterns in which bonds are formed between thiol of Cys and carbon or sulfur atoms of ligands, and nitrogen of Lys and carbon of ligands. Similar patterns were found for the coordination bonds. Hydrogen bonds occur in 67% of protein-organic compound complexes and 66% of them are formed between NH- group of protein residues and oxygen atom of ligands. We quantify relative abundance of specific interaction types and discuss their characteristic features. The extracted protein-organic compound patterns are shown to complement and improve a geometric approach for prediction of binding sites.

Conclusions and significance: We show that for a given type (group) of ligands and type of the interaction force, majority of protein-ligand interactions are repetitive and could be summarized with several simple atomic-level patterns. We summarize and analyze 10 frequently occurring interaction patterns that cover 56% of all considered complexes and we show a practical application for the patterns that concerns interactions with organic compounds.

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The residue groups that are coordinated by at least 10 metal ions and consist of 3 residues.
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pone-0004473-g005: The residue groups that are coordinated by at least 10 metal ions and consist of 3 residues.

Mentions: The residues which are coordinated by the same metal ion are grouped and we denote such groupings as the residue groups. We count the frequencies of the residue groups among different metal ions. For instance, given that Zn2+ forms coordination bonds with 4 Cys residues in 47 pockets, the corresponding frequency of (Cys)4 residue group is 47. The residue groups that are coordinated by at least 10 metal ions are shown in Figures 4, 5 and 6. The frequencies of residue groups that contain 5 or more residues are below 10 and thus they are not included in the above Figures. Total of 5 residue groups, i.e., (Cys)4, (Cys)3(His), (Cys)2(His)2, (Asp)2(His)2, and (Asp)(His)3, include 4 residues, see Figure 4. We observe that the (Cys)4 group is coordinated by the largest number of metal ions (47 metal ions). There are 11 residue groups that incorporate 3 residues, see Figure 5. These groups include (Cys)3, (Cys)1(His)2, (Asp)3, (Asp)2(Glu), (Asp)2(His), (Asp)(Glu)2, (Asp)(Glu)(His), (Asp)(His)2, (Glu)2(His), (Glu)(His)2 and (His)3. The (Asp)(His)2 and (His)3 groups are coordinated by the largest number of 44 and 38 metal ions, respectively. Finally, 6 residue groups, i.e., (Asp)2, (Asp)(Glu), (Asp)(His), (Glu)2, (Glu)(His) and (His)2, that make contact with 2 residues, see Figure 6.


Investigation of atomic level patterns in protein--small ligand interactions.

Chen K, Kurgan L - PLoS ONE (2009)

The residue groups that are coordinated by at least 10 metal ions and consist of 3 residues.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2637420&req=5

pone-0004473-g005: The residue groups that are coordinated by at least 10 metal ions and consist of 3 residues.
Mentions: The residues which are coordinated by the same metal ion are grouped and we denote such groupings as the residue groups. We count the frequencies of the residue groups among different metal ions. For instance, given that Zn2+ forms coordination bonds with 4 Cys residues in 47 pockets, the corresponding frequency of (Cys)4 residue group is 47. The residue groups that are coordinated by at least 10 metal ions are shown in Figures 4, 5 and 6. The frequencies of residue groups that contain 5 or more residues are below 10 and thus they are not included in the above Figures. Total of 5 residue groups, i.e., (Cys)4, (Cys)3(His), (Cys)2(His)2, (Asp)2(His)2, and (Asp)(His)3, include 4 residues, see Figure 4. We observe that the (Cys)4 group is coordinated by the largest number of metal ions (47 metal ions). There are 11 residue groups that incorporate 3 residues, see Figure 5. These groups include (Cys)3, (Cys)1(His)2, (Asp)3, (Asp)2(Glu), (Asp)2(His), (Asp)(Glu)2, (Asp)(Glu)(His), (Asp)(His)2, (Glu)2(His), (Glu)(His)2 and (His)3. The (Asp)(His)2 and (His)3 groups are coordinated by the largest number of 44 and 38 metal ions, respectively. Finally, 6 residue groups, i.e., (Asp)2, (Asp)(Glu), (Asp)(His), (Glu)2, (Glu)(His) and (His)2, that make contact with 2 residues, see Figure 6.

Bottom Line: Similar patterns were found for the coordination bonds.We show that for a given type (group) of ligands and type of the interaction force, majority of protein-ligand interactions are repetitive and could be summarized with several simple atomic-level patterns.We summarize and analyze 10 frequently occurring interaction patterns that cover 56% of all considered complexes and we show a practical application for the patterns that concerns interactions with organic compounds.

View Article: PubMed Central - PubMed

Affiliation: Department of Electrical and Computer Engineering, University of Alberta, Edmonton, Alberta, Canada.

ABSTRACT

Background: Shape complementarity and non-covalent interactions are believed to drive protein-ligand interaction. To date protein-protein, protein-DNA, and protein-RNA interactions were systematically investigated, which is in contrast to interactions with small ligands. We investigate the role of covalent and non-covalent bonds in protein-small ligand interactions using a comprehensive dataset of 2,320 complexes.

Methodology and principal findings: We show that protein-ligand interactions are governed by different forces for different ligand types, i.e., protein-organic compound interactions are governed by hydrogen bonds, van der Waals contacts, and covalent bonds; protein-metal ion interactions are dominated by electrostatic force and coordination bonds; protein-anion interactions are established with electrostatic force, hydrogen bonds, and van der Waals contacts; and protein-inorganic cluster interactions are driven by coordination bonds. We extracted several frequently occurring atomic-level patterns concerning these interactions. For instance, 73% of investigated covalent bonds were summarized with just three patterns in which bonds are formed between thiol of Cys and carbon or sulfur atoms of ligands, and nitrogen of Lys and carbon of ligands. Similar patterns were found for the coordination bonds. Hydrogen bonds occur in 67% of protein-organic compound complexes and 66% of them are formed between NH- group of protein residues and oxygen atom of ligands. We quantify relative abundance of specific interaction types and discuss their characteristic features. The extracted protein-organic compound patterns are shown to complement and improve a geometric approach for prediction of binding sites.

Conclusions and significance: We show that for a given type (group) of ligands and type of the interaction force, majority of protein-ligand interactions are repetitive and could be summarized with several simple atomic-level patterns. We summarize and analyze 10 frequently occurring interaction patterns that cover 56% of all considered complexes and we show a practical application for the patterns that concerns interactions with organic compounds.

Show MeSH