Results obtained on initial dataset of 100 complexes.A simple test of the effectiveness of a docking program is to take a protein-ligand complex from the Brookhaven Protein Data Bank and extract the ligand. The docking program can then be used to predict the binding mode of the ligand and a comparison made with the crystallographically observed position. This methodology has been used to validate GOLD. Tests were done in two phases: first, on a test set of 100 complexes; later, on an additional 34 complexes as a check against over-training. Results of these two test phases are summarised below.
Results of experiments on an initial dataset of 100 PDB complexes.
These experiments are described in G. Jones, P. Willett, R. C. Glen, A. R. Leach & R. Taylor, J. Mol. Biol 267 (1997) 727-748 and were first presented at Molecular Interactions, the 15th Annual Conference and AGM of the Molecular Graphics and Modelling Society, University of York, UK, 16-19 April 1996.
The method used for each test calculation was as follows. Parts of the protein remote from the binding site were deleted, in order to speed up the calculation. Enough of the protein was retained to ensure that all residues were present that might reasonably interact with the ligand. The ligand was extracted from the protein binding site. Hydrogens were placed on both the protein and the ligand in order to ensure that ionisation and tautomeric states were defined unambiguously. Obviously, this sometimes involved making hypotheses about the protonation states of residues such as His, Glu and Asp. The ligand was minimised into a low-energy conformation and the atom types of both the protein and ligand checked for accuracy.
In almost all test runs, all water molecules were deleted from the protein structure. This is not strictly defensible since water molecules often mediate protein-ligand binding. However, if more careful judgements were made on which waters to remove, the effect would be to improve the accuracy of the GOLD predictions. Hence, the deletion of all waters is a conservative strategy which will make GOLD look less reliable than it really is, rather than more reliable.
20 GA runs were performed on each test complex, using the default GA parameter settings.
Results obtained on initial dataset of 100 complexes.
Results of experiments on a subsequent dataset of 34 PDB complexes.
The GOLD algorithm was improved in various ways following the above set of validation tests. Some time later, therefore, a second set of tests was performed on 34 additional complexes in order to ensure that GOLD had not been over-trained on the original set.
Results obtained on an additional dataset of 34
complexes.
Pictures of dockings generated by GOLD.
The images in this page may take a while to load!
Some pictures of GOLD experiments.
Back to the main GOLD page