FITTED (Software)

The program covers covalent docking, metalloprotein docking, docking to nucleic acids, and flexible protein side chains. FITTED is the docking software of the Forecaster drug discovery platform. Common applications of FITTED include large-scale virtual screening, hit generation, and lead optimization.
==Features and applications==
FITTED is based on a Lamarckian genetic algorithm (GA) that uses a conjugate-gradient optimization method for local searches. The GA accounts for the flexibility of the ligand and the macromolecule through crossover and mutations of side chain and backbone conformations, as well as the presence of bridging water molecules.
FITTED can dock ligands to metalloenzymes by using quantum mechanics (QM)-derived parameters and functions to describe the coordination geometry and atomic charge variability around the metal (Zinc, Iron, or Magnesium). To describe the ligand-metal coordination process, a potential acid-base reaction between the ligand and a neighboring residue is considered when necessary.
FITTED can dock ligands covalently. The program automatically identifies and assigns the ligand covalent warhead atoms. A covalent bond will be formed during docking only if the warhead is predicted to be in close proximity to the targeted residue. If no covalent docking binding pose is found to be energetically-favored, the ligand is docked non-covalently.
===Drug discovery===
FITTED can be applied to find binders and inhibitors for a variety of targets.
Including:
* Covalent inhibitors targeting SARS-CoV-2 3CLpro
* Covalent and non-covalent inhibitors for prolyl oligopeptidase (POP) and fibroblast activation protein α (FAP)
* Hepatitis C virus (HCV) polymerase inhibitors
* Histone deacetylase (HDAC) inhibitors
* G-quadruplex binders
===Accuracy===
The latest reported accuracy of FITTED (June 2021) is ~70% for self-docking (RMSD cutoff of 2.0Å) and ~50% for cross-docking (RMSD cutoff of 2.5Å) when the top 3 binding modes are considered. The accuracy for metalloprotein self-docking (magnesium and iron) is ~50%. When the top 10 binding modes are considered, FITTED identifies the correct binding mode in 90% of the cases.
==History and Use==
In 2015, a study by Xu et al. comparing 8 molecular docking programs and 16 different scoring functions for predicting the biological activities of ligands for protein targets found that FITTED, FlexX and GOLDScore outperformed the rest of the tested programs.
In 2018, a study by Scarpino et al. evaluated six covalent docking programs and found that FITTED was capable of recovering 56% of experimental binding modes in the Top 1 predicted poses and 81% in the Top 10. 
==Supported operating systems==
FITTED can be run on Windows, Linux, and MacOS, as part of the Forecaster drug discovery platform. A Java-based graphical user interface (GUI) is provided for all operating systems.
===Licensing===
FITTED is distributed as part of the Forecaster drug discovery platform by Molecular Forecaster Inc, company located in Montreal, Canada. The Forecaster drug discovery platform is free for academia, while industrial users must purchase a license.
Category:Software
Category:Genetic algorithms
Category:2015 software
Category:Programs