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.
- Fully Automated Wizard simplifies workflow.
- Task Based Interface streamlines work environment.
- 2D and 3D Molecular Editor
- Molecule Searching Ability to see if it has been previously named.
- Automatic Covalent Detection
- Automatic Ligand Fitting automatically fits low energy conformations of the ligand to density, typically in less than one minute. This task can be performed via the GUI or a command line application.
- Refinement Dictionary Generation uses MMFF94. REFMAC and CNX formats are currently supported. This task can be performed via the GUI or a command line application.
- Performance retained with flexible molecules (e.g. ≤ 20 rotatable bonds) and poor density (e.g. resolution ≤ 3.5 Å).
- Coot integration with both the GUI and command line applications.