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AFITT includes both fully automated and interactive solutions for real-space fitting of ligands in Protein-Ligand complexes.
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 since it was founded, specifically conformer generation, shape potential, structure minimization with high quality small molecule force field 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 [1].
AFITT distributions come with both a GUI and command-line applications. The GUI allows users to interactively perform automatic ligand-fitting, manual protein modeling 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.
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Crystal Stucture (in green) compared to AFITT solution. |
Interface is simple and intuitive. Note that multiple solutions are generated and ranked. |
Protein modeling mode show real-time real-space correlation in which larger halos indicate better fit |
Features:
- Automatic Ligand Fitting: given a ligand and an electron density map, AFITT 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.
- Semi-automated or manual Protein Modeling: allows residue fitting, manual torsion adjustment, best rotamer search and Ramachandran plot generation for validation.
- Refinement Dictionary Generation uses MMFF94s. 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)
- VIVANT compatibility: AFITT's 3D scenes, including density, can be "published" in PowerPoint®, Word® and web pages for both navigation through bookmarked scenes or live interaction.
- Coot integration with the command line applications.
[1] S. Wlodek, A. G. Skillman and A. Nicholls, Acta Crystallographica D, D62, pp. 741-749 (2006).
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