Docking Ligands into Flexible and Solvated Macromolecules. 3. Impact of Input Ligand Conformation, Protein Flexibility, and Water Molecules on the Accuracy of Docking Programs Export

@article{CorbeilM09, abstract = {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.}, author = {Corbeil, Christopher R. and Moitessier, Nicolas}, citeulike-article-id = {4281094}, citeulike-linkout-0 = {http://dx.doi.org/10.1021/ci8004176}, citeulike-linkout-1 = {http://pubs.acs.org/doi/abs/10.1021/ci8004176}, doi = {10.1021/ci8004176}, journal = {Journal of Chemical Information and Modeling}, keywords = {algorithm, conformational, displaceable, docking, enhanced, fitted26, flexibility, genetic, molecules, protein, ring, search, water}, number = {0}, posted-at = {2009-04-07 08:00:52}, priority = {2}, title = {Docking Ligands into Flexible and Solvated Macromolecules. 3. Impact of Input Ligand Conformation, Protein Flexibility, and Water Molecules on the Accuracy of Docking Programs}, url = {http://dx.doi.org/10.1021/ci8004176}, volume = {0}, year = {0000} }

TY - JOUR ID - CorbeilM09 L3 - citeulike-article-id:4281094 N2 - 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. IS - 0 JF - Journal of Chemical Information and Modeling TI - Docking Ligands into Flexible and Solvated Macromolecules. 3. Impact of Input Ligand Conformation, Protein Flexibility, and Water Molecules on the Accuracy of Docking Programs VL - 0 KW - algorithm KW - conformational KW - displaceable KW - docking KW - enhanced KW - fitted26 KW - flexibility KW - genetic KW - molecules KW - protein KW - ring KW - search KW - water AU - Corbeil, Christopher AU - Moitessier, Nicolas PY - 2000/// UR - http://dx.doi.org/10.1021/ci8004176 ER -