Docking Ligands into Flexible and Solvated Macromolecules. 3. Impact of Input Ligand Conformation, Protein Flexibility, and Water Molecules on the Accuracy of Docking Programs Christopher R. Corbeil Nicolas Moitessier 10.1021/ci8004176.s002 https://acs.figshare.com/articles/dataset/Docking_Ligands_into_Flexible_and_Solvated_Macromolecules_3_Impact_of_Input_Ligand_Conformation_Protein_Flexibility_and_Water_Molecules_on_the_Accuracy_of_Docking_Programs/2861263 Several modifications and additions to Fitted1.5 led to the development of Fitted2.6. Among the novel implementations are a matching algorithm-enhanced genetic algorithm and a ring conformational search algorithm. With these various optimizations, we also hoped to remove the biases and to develop a docking program that would provide results (i.e., poses) as independent as possible to the input ligand and protein conformations and used parameters, although keeping the options to provide additional experimental information. These biases were investigated within Fitted2.6 along with FlexX, GOLD, Glide, and Surflex. The input ligand conformation was found to have a major impact on the program accuracy as drops as large as 10−50% were observed with all the programs but Fitted. This comparative study also demonstrates that the accuracy of Fitted is similar to that of other widely used programs. We have also demonstrated that protein flexibility, displaceable water molecules, and ring conformational search algorithms, three of the main Fitted features, significantly increased its accuracy. Finally, we also proposed potential modifications to the available programs to further improve their accuracy in binding mode prediction. 2009-04-27 00:00:00 Protein Flexibility search algorithms Fitted 2.6. Solvated Macromolecules search algorithm 3. Impact Water Molecules docking program protein flexibility Input Ligand Conformation novel implementations displaceable water molecules Docking Ligands Docking ProgramsSeveral modifications binding mode prediction Fitted features input ligand conformation Fitted 1.5 input ligand Fitted 2.6 program accuracy protein conformations