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Binding ligand prediction for proteins using partial matching of local surface patches.

Sael L, Kihara D - Int J Mol Sci (2010)

Bottom Line: The surface patches are encoded with the 3D Zernike descriptors.Unlike the existing methods which compare global characteristics of the protein fold or the global pocket shape, the local surface patch method can find functional similarity between non-homologous proteins and binding pockets for flexible ligand molecules.The proposed method improves prediction results over global pocket shape-based method which was previously developed by our group.

View Article: PubMed Central - PubMed

Affiliation: Department of Computer Science, Purdue University, West Lafayette, IN 47907, USA; E-Mail: lee399@cs.purdue.edu.

ABSTRACT
Functional elucidation of uncharacterized protein structures is an important task in bioinformatics. We report our new approach for structure-based function prediction which captures local surface features of ligand binding pockets. Function of proteins, specifically, binding ligands of proteins, can be predicted by finding similar local surface regions of known proteins. To enable partial comparison of binding sites in proteins, a weighted bipartite matching algorithm is used to match pairs of surface patches. The surface patches are encoded with the 3D Zernike descriptors. Unlike the existing methods which compare global characteristics of the protein fold or the global pocket shape, the local surface patch method can find functional similarity between non-homologous proteins and binding pockets for flexible ligand molecules. The proposed method improves prediction results over global pocket shape-based method which was previously developed by our group.

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Related in: MedlinePlus

Examples of matching patch pairs in AMP, ATP, NAD and FAD binding pocket using the distance threshold 0.30. The matched pairs which locate at equivalent position to adenosine monophosphate are shown in the same color.
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f7-ijms-11-05009: Examples of matching patch pairs in AMP, ATP, NAD and FAD binding pocket using the distance threshold 0.30. The matched pairs which locate at equivalent position to adenosine monophosphate are shown in the same color.

Mentions: The surface patch method also identifies local similarities of different ligand binding pockets. One such example is adenosine monophosphate (adenine + ribose + phosphate) group shared by AMP, ATP, NAD, and FAD. Figure 7 shows matched patch pairs between four pockets, each of which binding AMP, ATP, NAD, and FAD. Patches of the same color locate at equivalent positions relative to adenosine monophosphate. The blue patches in the four pockets are all located at the phosphate binding region, the magenta patches are at the ribose region and the yellow patches are all located at the adenine region of the bound ligand. Local surface matches in different types of pockets can deteriorate the binding ligand prediction in the current benchmark test. Indeed, when ATP binding pockets are queried against the benchmark dataset, AMP comes within Top-3 prediction in six out of nine cases, and five out of fourteen cases of searches from AMP binding pockets retrieve ATP within Top-3. Similarly, when FAD binding pockets are queried, NAD shows up within Top-3 for all of the ten cases, while seven out of fifteen cases FAD is within Top-3 prediction when NAD binding pockets are queried. The method does not confuse between ATP/AMP and FAD/NAD since their pocket sizes are largely different (Table 1).


Binding ligand prediction for proteins using partial matching of local surface patches.

Sael L, Kihara D - Int J Mol Sci (2010)

Examples of matching patch pairs in AMP, ATP, NAD and FAD binding pocket using the distance threshold 0.30. The matched pairs which locate at equivalent position to adenosine monophosphate are shown in the same color.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3100846&req=5

f7-ijms-11-05009: Examples of matching patch pairs in AMP, ATP, NAD and FAD binding pocket using the distance threshold 0.30. The matched pairs which locate at equivalent position to adenosine monophosphate are shown in the same color.
Mentions: The surface patch method also identifies local similarities of different ligand binding pockets. One such example is adenosine monophosphate (adenine + ribose + phosphate) group shared by AMP, ATP, NAD, and FAD. Figure 7 shows matched patch pairs between four pockets, each of which binding AMP, ATP, NAD, and FAD. Patches of the same color locate at equivalent positions relative to adenosine monophosphate. The blue patches in the four pockets are all located at the phosphate binding region, the magenta patches are at the ribose region and the yellow patches are all located at the adenine region of the bound ligand. Local surface matches in different types of pockets can deteriorate the binding ligand prediction in the current benchmark test. Indeed, when ATP binding pockets are queried against the benchmark dataset, AMP comes within Top-3 prediction in six out of nine cases, and five out of fourteen cases of searches from AMP binding pockets retrieve ATP within Top-3. Similarly, when FAD binding pockets are queried, NAD shows up within Top-3 for all of the ten cases, while seven out of fifteen cases FAD is within Top-3 prediction when NAD binding pockets are queried. The method does not confuse between ATP/AMP and FAD/NAD since their pocket sizes are largely different (Table 1).

Bottom Line: The surface patches are encoded with the 3D Zernike descriptors.Unlike the existing methods which compare global characteristics of the protein fold or the global pocket shape, the local surface patch method can find functional similarity between non-homologous proteins and binding pockets for flexible ligand molecules.The proposed method improves prediction results over global pocket shape-based method which was previously developed by our group.

View Article: PubMed Central - PubMed

Affiliation: Department of Computer Science, Purdue University, West Lafayette, IN 47907, USA; E-Mail: lee399@cs.purdue.edu.

ABSTRACT
Functional elucidation of uncharacterized protein structures is an important task in bioinformatics. We report our new approach for structure-based function prediction which captures local surface features of ligand binding pockets. Function of proteins, specifically, binding ligands of proteins, can be predicted by finding similar local surface regions of known proteins. To enable partial comparison of binding sites in proteins, a weighted bipartite matching algorithm is used to match pairs of surface patches. The surface patches are encoded with the 3D Zernike descriptors. Unlike the existing methods which compare global characteristics of the protein fold or the global pocket shape, the local surface patch method can find functional similarity between non-homologous proteins and binding pockets for flexible ligand molecules. The proposed method improves prediction results over global pocket shape-based method which was previously developed by our group.

Show MeSH
Related in: MedlinePlus