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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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The dependence on the partial disorder as judged by the ratio of the standard deviation of ligand ADPs to their mean value. The total test set is in a darker colour; ‘good’ ligands are in a lighter colour.
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fig9: The dependence on the partial disorder as judged by the ratio of the standard deviation of ligand ADPs to their mean value. The total test set is in a darker colour; ‘good’ ligands are in a lighter colour.

Mentions: In addition to the mean value of ADPs, we investigated the effect of partial ligand disorder using the ratio of the standard deviation of ADPs within the reference ligand over their mean value as an indicator (D),The dependence on this is displayed in Fig. 9 ▶. The site-identification step is essentially unaffected by partially disordered ligand atoms, except in cases where the value of D is close to zero (the first bin in Fig. 9 ▶). Although this may look surprising at a first glance, these largely represent cases where the ligand ADPs were set to the same value and possibly not fully refined. This might have been caused by poorly defined electron density, for example. The other reason is related to the way the ADPs are refined. Typically, restraints are used to make the B factors of neighbouring atoms similar. The degree of similarity is expressed in absolute rather than relative units. Thus, a model with high mean ADP would have a lower value of D compared with a model with low ADPs. This may lead to a poorer description of the ligand binding than in the PDB and result in lower map correlation coefficients.


Assessment of automatic ligand building in ARP/wARP.

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

The dependence on the partial disorder as judged by the ratio of the standard deviation of ligand ADPs to their mean value. 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

fig9: The dependence on the partial disorder as judged by the ratio of the standard deviation of ligand ADPs to their mean value. The total test set is in a darker colour; ‘good’ ligands are in a lighter colour.
Mentions: In addition to the mean value of ADPs, we investigated the effect of partial ligand disorder using the ratio of the standard deviation of ADPs within the reference ligand over their mean value as an indicator (D),The dependence on this is displayed in Fig. 9 ▶. The site-identification step is essentially unaffected by partially disordered ligand atoms, except in cases where the value of D is close to zero (the first bin in Fig. 9 ▶). Although this may look surprising at a first glance, these largely represent cases where the ligand ADPs were set to the same value and possibly not fully refined. This might have been caused by poorly defined electron density, for example. The other reason is related to the way the ADPs are refined. Typically, restraints are used to make the B factors of neighbouring atoms similar. The degree of similarity is expressed in absolute rather than relative units. Thus, a model with high mean ADP would have a lower value of D compared with a model with low ADPs. This may lead to a poorer description of the ligand binding than in the PDB and result in lower map correlation coefficients.

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