ADDock has numerous advantages

 

With high accuracy and discriminative ability, the new docking method ADDock fulfills the criteria of being an efficient docking method. To reduce the RMSD or improve the docking accuracy for the badly docked complexes by ADDock, we can gradually increase the GA steps from 20000 to 640000. The docking speed by ADDock is reasonably quick since it takes about 126 s on a HP workstation running with 1.5 GHz Intel itanium2 processor to complete a docking of 40000 GA steps for ligands consisted of 50 atoms. With its discriminative ability, ADDock can be used to rank the compounds collected from a preliminary screening.

 

To rank the random compounds screened, ADDock takes the docking energies computed for each compound as the major criterion. These are the steric interaction energies computed between the docked conformation generated from GA and the receptor active site. ADDock is able to discriminate good from bad docking ligands among some non-native ligands docked even for ligands of the same molecular size or smaller than that of the native ligand of a receptor.

The probability for docking ligands accurately by ADDock relies on the selection of an anchor and a random seed number entered at the beginning. Selection of an anchor is much more important than entering a random number at the beginning. Since no translational motion for ligands is implemented, ligand atoms deeply bound inside the receptor active site are chosen as anchors. With the same random number entered, the probability for being accurately docked by ADDock for an anchor chosen will be quite different from that for a different anchor chosen. We find that some of the badly docked ligands by ADDock are loosely bound with their corresponding receptors. The g/a (size of active site/size of ligand) ratio computed for these complexes are somewhat larger than those computed for the accurately docked ones. In this regard, ADDock agrees with those reported in literature that it is rather difficult to accurately dock a ligand that is loosely bound in a large receptor active site.

The binary rather than decimal encoding is used in ADDock for evolving the GA parameters because the former can be more efficiently implemented than the latter for the current parameter settings. The GA parameters such as crossover and mutation probabilities are determined by some preliminary runs and are fixed throughout the docking process. To obtain greater docking accuracy by ADDock, the GA steps are literally increased while keeping all the GA parameters fixed.