Automatic Ligand Fitting to Crystallographic Density
AFITT is the only software to offer a fully automatic ligand fitting process that optimizes a real-space fit to density while keeping conformational strain to a minimum. It capitalizes on a combination of core technologies that OpenEye has developed, specifically conformer generation, shape potential, high quality small molecule structure minimization, and visualization. The key step, after finding the appropriate conformers and aligning them to density, is the implementation of a refinement that combines force field and shape potentials, via a series of adiabatic optimizations .
The AFITT distribution includes both a GUI and a collection of command-line applications. The GUI allows users to interactively perform automatic ligand-fitting, and refinement dictionary generation. In addition, the command-line tools provide a powerful means for integration and automation, which is critical in the application of high-throughput crystallography for drug discovery.
|Crystal structure (in green) compared to AFITT solution||Multiple solutions are generated and ranked.||Interactive 3D molecular editing in context of electron densitry.|
- Fast automatic ligand fitting process fits low energy ligand conformations to density, typically in less than a minute
- Multiple chemical forcefields available for tricky ligands (MMFF94, PM3)
- Automatic (optional) re-fitting of side chains to density using several methods
- Fully automated wizard simplifies workflow
- Task based interface streamlines work environment
- 2D and 3D molecular editor
- Search ligands to determine if it they been previously deposited and report conflicts if they don't match
- Automatic covalent detection
- Refinement dictionary generation for REFMAC, PHENIX, and CNX using MMFF94
- Excellent performance even with flexible molecules (≤ 20 rotatable bonds) and poor density (resolution ≤ 3.5 Å)
- Integrates with Coot
- Automated Ligand placement and refinement with a combined force field and shape potential, S. Wlodek, A.G. Skillman, A. Nicholls. Acta Cryst. D., 2006, 62, 741.