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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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Related in: MedlinePlus

Effect of the average ligand atomic displacement parameter on the efficiency of the procedure. The total test set is in a darker colour; ‘good’ ligands are in a lighter colour.
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fig8: Effect of the average ligand atomic displacement parameter on the efficiency of the procedure. The total test set is in a darker colour; ‘good’ ligands are in a lighter colour.

Mentions: The disorder of the atoms in the ligand molecule can be estimated by a variety of metrics. We used the average ADP (‘ligand B factor’) taken from the deposited structures and observed that its increase negatively affects both the identification of the ligand site and the ligand construction (Fig. 8 ▶). Particularly high ligand B factors (above 40 Å2) bring the performance below the average for the total set. It is understandable that sites with very mobile poorly ordered (and therefore hardly present) ligands are more problematic to identify. In such sites the electron-density cluster is spread much more widely and flatly than for ordered ligands, where it peaks around atomic positions. As a result, given the same volume, the correct cluster becomes indistinguishable from competing density features: other ligands, solvent or noise. Indeed, the cases of ‘good’ ligands do not show such a sharp falloff with the increase of the ligand B factor. Concurrently, these are largely the ligands with higher mean B factor, which have a poorer real-space map correlation coefficient and did not qualify for our subset of ‘good’ ligands.


Assessment of automatic ligand building in ARP/wARP.

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

Effect of the average ligand atomic displacement parameter on the efficiency of the procedure. The total test set is in a darker colour; ‘good’ ligands are in a lighter colour.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig8: Effect of the average ligand atomic displacement parameter on the efficiency of the procedure. The total test set is in a darker colour; ‘good’ ligands are in a lighter colour.
Mentions: The disorder of the atoms in the ligand molecule can be estimated by a variety of metrics. We used the average ADP (‘ligand B factor’) taken from the deposited structures and observed that its increase negatively affects both the identification of the ligand site and the ligand construction (Fig. 8 ▶). Particularly high ligand B factors (above 40 Å2) bring the performance below the average for the total set. It is understandable that sites with very mobile poorly ordered (and therefore hardly present) ligands are more problematic to identify. In such sites the electron-density cluster is spread much more widely and flatly than for ordered ligands, where it peaks around atomic positions. As a result, given the same volume, the correct cluster becomes indistinguishable from competing density features: other ligands, solvent or noise. Indeed, the cases of ‘good’ ligands do not show such a sharp falloff with the increase of the ligand B factor. Concurrently, these are largely the ligands with higher mean B factor, which have a poorer real-space map correlation coefficient and did not qualify for our subset of ‘good’ ligands.

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