Ligand identification using electron-density map correlations.
A procedure for the identification of ligands bound in crystal structures of macromolecules is described. Two characteristics of the density corresponding to a ligand are used in the identification procedure. One is the correlation of the ligand density with each of a set of test ligands after optimization of the fit of that ligand to the density. The other is the correlation of a fingerprint of the density with the fingerprint of model density for each possible ligand. The fingerprints consist of an ordered list of correlations of each the test ligands with the density. The two characteristics are scored using a Z-score approach in which the correlations are normalized to the mean and standard deviation of correlations found for a variety of mismatched ligand-density pairs, so that the Z scores are related to the probability of observing a particular value of the correlation by chance. The procedure was tested with a set of 200 of the most commonly found ligands in the Protein Data Bank, collectively representing 57% of all ligands in the Protein Data Bank. Using a combination of these two characteristics of ligand density, ranked lists of ligand identifications were made for representative (F(o) - F(c))exp(i(phi)c) difference density from entries in the Protein Data Bank. In 48% of the 200 cases, the correct ligand was at the top of the ranked list of ligands. This approach may be useful in identification of unknown ligands in new macromolecular structures as well as in the identification of which ligands in a mixture have bound to a macromolecule.
Terwilliger
Thomas C
TC
Los Alamos National Laboratory, Mailstop M888, Los Alamos, NM 87545, USA. terwilliger@lanl.gov
Adams
Paul D
PD
Moriarty
Nigel W
NW
Cohn
Judith D
JD
D000465:Algorithms; D000818:Animals; D001429:Bacteriochlorophylls / Q000737:chemistry; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods*; D018360:Crystallography, X-Ray; D030562:Databases, Protein; D004583:Electrons; D006801:Humans; D008024:Ligands; D046911:Macromolecular Substances; D008968:Molecular Conformation; D011336:Probability; D011485:Protein Binding; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry
D001429:Bacteriochlorophylls; D008024:Ligands; D046911:Macromolecular Substances; D011506:Proteins