Theoretical and Computational Chemistry

Docking Ligands into Flexible and Solvated Macromolecules. 8. Forming New Bonds – Challenges and Opportunities.


Over the years, structure-based design programs and specifically docking small molecules to proteins have become prominent in drug discovery. However, many of these computational tools have been developed to primarily dock enzyme inhibitors (and ligand to other protein classes) relying heavily on hydrogen bonds, electrostatic and hydrophobic interactions. In reality, many drug targets either feature metal ions, can be targeted covalently, or are simply not even proteins (e.g., nucleic acids). Herein, we describe several new features that we have implemented into FITTED to broaden its applicability to a wide range of covalent enzyme inhibitors, and to metalloenzymes, where metal coordination is essential for drug binding. We also report new datasets that were essential demonstrate areas of success and those where additional efforts are required. This resource could be used by other program developers to assess their own

Version notes

Version 1.0


Thumbnail image of Moitessier-ChemRXiv-FITTED.pdf
download asset Moitessier-ChemRXiv-FITTED.pdf 1 MB [opens in a new tab]

Supplementary material

Thumbnail image of Moitessier-ChemRXiv-FITTED2021-SuppInf.pdf
download asset Moitessier-ChemRXiv-FITTED2021-SuppInf.pdf 1 MB [opens in a new tab]