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Assessment of automatic ligand building in ARP/wARP.

Evrard GX, Langer GG, Perrakis A, Lamzin VS - Acta Crystallogr. D Biol. Crystallogr. (2006)

Bottom Line: Ligand building in ARP/wARP involves two main steps: automatic identification of the location of the ligand and the actual construction of its atomic model.The first step is most successful for large ligands.Both steps are successful for ligands with low to moderate atomic displacement parameters.

View Article: PubMed Central - HTML - PubMed

Affiliation: European Molecular Biology Laboratory (EMBL), c/o DESY, Notkestrasse 85, 22603 Hamburg, Germany. evrard@embl-hamburg.de

ABSTRACT
The efficiency of the ligand-building module of ARP/wARP version 6.1 has been assessed through extensive tests on a large variety of protein-ligand complexes from the PDB, as available from the Uppsala Electron Density Server. Ligand building in ARP/wARP involves two main steps: automatic identification of the location of the ligand and the actual construction of its atomic model. The first step is most successful for large ligands. The second step, ligand construction, is more powerful with X-ray data at high resolution and ligands of small to medium size. Both steps are successful for ligands with low to moderate atomic displacement parameters. The results highlight the strengths and weaknesses of both the method of ligand building and the large-scale validation procedure and help to identify means of further improvement.

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Efficiency of the identification of the binding site in the presence of other smaller (R                  size > 1) or larger (R                  size < 1) ligands.
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fig10: Efficiency of the identification of the binding site in the presence of other smaller (R size > 1) or larger (R size < 1) ligands.

Mentions: Based on the design of the procedure, when a mixture of ligand types is present, ligand-binding sites are most successfully identified for the largest ligand type. This behaviour is captured in Fig. 10 ▶. The success of identifying the location of a ligand is strongly correlated with the ratio R size, which we define as the ratio of the size of the ligand to be built to the size of the largest of the remaining ligands bound to the protein. For values of R size that are lower than one, i.e. an attempt to build a ligand that is not the largest in the structure, the likelihood of correct site identification rapidly approaches zero. At the same time, in a considerable number of cases the location is still correctly identified, particularly when R size is within the range 0.8–1.0. The reason for this probably lies in the search of the optimal density threshold ρthres, where the cluster for a smaller ligand may survive an increase of the contour level at nearly the same volume, whereas the density for a competing larger entity may break into unconnected pieces. Fig. 10 ▶ also shows that even for the search of the largest ligands, the success rate for the correct identification of the binding site is still dependent on the size contrast between competing ligands. Given a noisy electron-density map, the clusters corresponding to similarly sized but different ligands may become indistinguishable just by their volume.


Assessment of automatic ligand building in ARP/wARP.

Evrard GX, Langer GG, Perrakis A, Lamzin VS - Acta Crystallogr. D Biol. Crystallogr. (2006)

Efficiency of the identification of the binding site in the presence of other smaller (R                  size > 1) or larger (R                  size < 1) ligands.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2483501&req=5

fig10: Efficiency of the identification of the binding site in the presence of other smaller (R size > 1) or larger (R size < 1) ligands.
Mentions: Based on the design of the procedure, when a mixture of ligand types is present, ligand-binding sites are most successfully identified for the largest ligand type. This behaviour is captured in Fig. 10 ▶. The success of identifying the location of a ligand is strongly correlated with the ratio R size, which we define as the ratio of the size of the ligand to be built to the size of the largest of the remaining ligands bound to the protein. For values of R size that are lower than one, i.e. an attempt to build a ligand that is not the largest in the structure, the likelihood of correct site identification rapidly approaches zero. At the same time, in a considerable number of cases the location is still correctly identified, particularly when R size is within the range 0.8–1.0. The reason for this probably lies in the search of the optimal density threshold ρthres, where the cluster for a smaller ligand may survive an increase of the contour level at nearly the same volume, whereas the density for a competing larger entity may break into unconnected pieces. Fig. 10 ▶ also shows that even for the search of the largest ligands, the success rate for the correct identification of the binding site is still dependent on the size contrast between competing ligands. Given a noisy electron-density map, the clusters corresponding to similarly sized but different ligands may become indistinguishable just by their volume.

Bottom Line: Ligand building in ARP/wARP involves two main steps: automatic identification of the location of the ligand and the actual construction of its atomic model.The first step is most successful for large ligands.Both steps are successful for ligands with low to moderate atomic displacement parameters.

View Article: PubMed Central - HTML - PubMed

Affiliation: European Molecular Biology Laboratory (EMBL), c/o DESY, Notkestrasse 85, 22603 Hamburg, Germany. evrard@embl-hamburg.de

ABSTRACT
The efficiency of the ligand-building module of ARP/wARP version 6.1 has been assessed through extensive tests on a large variety of protein-ligand complexes from the PDB, as available from the Uppsala Electron Density Server. Ligand building in ARP/wARP involves two main steps: automatic identification of the location of the ligand and the actual construction of its atomic model. The first step is most successful for large ligands. The second step, ligand construction, is more powerful with X-ray data at high resolution and ligands of small to medium size. Both steps are successful for ligands with low to moderate atomic displacement parameters. The results highlight the strengths and weaknesses of both the method of ligand building and the large-scale validation procedure and help to identify means of further improvement.

Show MeSH
Related in: MedlinePlus