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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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Effect of resolution of the X-ray data 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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fig7: Effect of resolution of the X-ray data on the efficiency of the procedure. The total test set is in a darker colour; ‘good’ ligands are in a lighter colour.

Mentions: The effect of the resolution of the diffraction data used for the refinement and subsequent construction of the density maps is shown in Fig. 7 ▶. The resolution barely influences the success of the identification of the ligand-binding site. This is to be expected, since the volume corresponding to the ligand-density cluster remains almost unaffected by series-termination effects. However, at very high resolution (1.0 Å and higher) the chances of correct identification of the binding site are lowered. The underlying reason lies in the fact that at such a resolution the atomic features in the density and the fluctuation of the density height along interatomic bonds are very strong. For a value of ρthres higher than about 1σ the ligand density is almost always broken into several disconnected small pieces. At a lower threshold the ligand-density cluster is solid but its volume may be of similar size to the volume of density clusters that are located elsewhere and originate from noise, excluded solvent etc. This complicates the search of the binding site immensely. In addition, owing to the scarceness of our test set in the resolution range higher than 1.0 Å, these structures have not been taken into account.


Assessment of automatic ligand building in ARP/wARP.

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

Effect of resolution of the X-ray data 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

fig7: Effect of resolution of the X-ray data on the efficiency of the procedure. The total test set is in a darker colour; ‘good’ ligands are in a lighter colour.
Mentions: The effect of the resolution of the diffraction data used for the refinement and subsequent construction of the density maps is shown in Fig. 7 ▶. The resolution barely influences the success of the identification of the ligand-binding site. This is to be expected, since the volume corresponding to the ligand-density cluster remains almost unaffected by series-termination effects. However, at very high resolution (1.0 Å and higher) the chances of correct identification of the binding site are lowered. The underlying reason lies in the fact that at such a resolution the atomic features in the density and the fluctuation of the density height along interatomic bonds are very strong. For a value of ρthres higher than about 1σ the ligand density is almost always broken into several disconnected small pieces. At a lower threshold the ligand-density cluster is solid but its volume may be of similar size to the volume of density clusters that are located elsewhere and originate from noise, excluded solvent etc. This complicates the search of the binding site immensely. In addition, owing to the scarceness of our test set in the resolution range higher than 1.0 Å, these structures have not been taken into account.

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