Small-molecule protein docking is an essential tool in drug design and to understand molecular recognition. Our group is responsible for the development of FlexAID36. FlexAID, is a docking algorithm that can use small-molecules and peptides as ligands and proteins/nucleic acids as targets. It permits full ligand flexibility as well as target side-chain flexibility. FlexAID utilizes a soft scoring function, i.e. one that is not highly dependent on specific geometric criteria, based on surface complementarity. The energy parameters of the scoring function were derived from the classification of a large dataset of native and near native (less than 2Å RMSD) conformations for nearly 1500 complexes from the PDBbind database as true positive examples. These were countered over successive rounds of Monte Carlo optimization over an ever increasing and successively more difficult sets (increasingly lower energy decoys) with RMSD above 2Å. FlexAID has been used in numerous projects in collaborations and in our group.

FlexAID has been shown to outperform existing widely used software such as AutoDock Vina and FlexX in the prediction of binding poses. This is particularly true in cases where target flexibility is crucial, such as is likely to be the case when using homology models.

In the image above, two versions of FlexAID (standard and one implementing entropy concepts in scoring, denoted by ds) are compared to three different existing widely used software in cross-docking simulations, that is, simulations where the target structure was not crystallized with the ligand of interest). Two cases are studies, with and without target side-chain flexibility, full ligand flexibility in both cases. The software are compared using two different datasets, the standard widely used (and easier) Astex dataset as well as the HAP2 dataset25 where side-chain flexibility is critical.

You may find some of our recent published applications of FlexAID in the publications section. FlexAID can be used programatically but it can also be used through the NRGsuite graphical user interface. For large scale applications (as in virtual screening) it is better to use it programatically. For individual molecules (such as in structure-based drug design) it may be easier to use it through the NRGsuite.

FlexAID Code and executables (version 2.48): Source code, Linux 32-bit, Linux 64-bit, Windows 32-bit, Windows 64-bit, MacOSX 64-bit.