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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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Distribution of the local map correlation for the test sample of 3369 single largest fully occupied ligands. Those belonging to a ‘good’ ligand subset are indicated by a curly bracket. The colour coding indicating ligand-building results is the same as in Fig. 5 ▶.
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fig3: Distribution of the local map correlation for the test sample of 3369 single largest fully occupied ligands. Those belonging to a ‘good’ ligand subset are indicated by a curly bracket. The colour coding indicating ligand-building results is the same as in Fig. 5 ▶.

Mentions: The success of any ligand-building procedure strongly depends on the quality of the density map of the ligand looked for. A number of factors affecting this (resolution of the data, ligand size and its ADPs) are discussed in the following sections. Here, we address the point of how good the electron density is overall. Clearly, for a ligand that is hardly bound at all, an attempt to find it would very much seem like Charles Darwin’s blind man looking for a black cat in a dark room when the cat is not actually there. As a measure of the overall quality of the blob of the ligand density, we used a real-space map correlation coefficient (RSMCC) of the density calculated from the deposited reference ligand to the difference electron-density map computed from the X-ray data. The ‘calculated’ density was computed using the coordinates, ADP and atomic types of the reference ligand. An additional artificial exponential term was added to model series terminations. RSMCC was computed on all density grid points that were within 1.9 Å distance of ligand atoms. Fig. 3 ▶ displays the distribution of RSMCC for the total test set of single largest and fully occupied ligand-building cases.


Assessment of automatic ligand building in ARP/wARP.

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

Distribution of the local map correlation for the test sample of 3369 single largest fully occupied ligands. Those belonging to a ‘good’ ligand subset are indicated by a curly bracket. The colour coding indicating ligand-building results is the same as in Fig. 5 ▶.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig3: Distribution of the local map correlation for the test sample of 3369 single largest fully occupied ligands. Those belonging to a ‘good’ ligand subset are indicated by a curly bracket. The colour coding indicating ligand-building results is the same as in Fig. 5 ▶.
Mentions: The success of any ligand-building procedure strongly depends on the quality of the density map of the ligand looked for. A number of factors affecting this (resolution of the data, ligand size and its ADPs) are discussed in the following sections. Here, we address the point of how good the electron density is overall. Clearly, for a ligand that is hardly bound at all, an attempt to find it would very much seem like Charles Darwin’s blind man looking for a black cat in a dark room when the cat is not actually there. As a measure of the overall quality of the blob of the ligand density, we used a real-space map correlation coefficient (RSMCC) of the density calculated from the deposited reference ligand to the difference electron-density map computed from the X-ray data. The ‘calculated’ density was computed using the coordinates, ADP and atomic types of the reference ligand. An additional artificial exponential term was added to model series terminations. RSMCC was computed on all density grid points that were within 1.9 Å distance of ligand atoms. Fig. 3 ▶ displays the distribution of RSMCC for the total test set of single largest and fully occupied ligand-building cases.

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