SZYBKI consists of 4 applications that carry out force field calculations on small molecule ligands or protein-ligand complexes with small molecule ligands. The main program, SZYBKI, is a general-purpose program with a wide spectrum of force field functionalities. Input for SZYBKI is all-atom molecular structures for the ligands (and, if desired, protein) with plausible 3-dimensional atomic coordinates. The other program, Freeform, calculates some thermodynamic properties, useful for drug discovery, for small molecules. Input for Freeform is a file of molecular structures for the ligands in a variety of formats ranging from SMILES strings to all-atom multiconformer formats. The output from both programs is all-atom molecular structures with associated information in the log output on the details of the calculations.
The SZYBKI distribution comprises 2 applications:
Performs force field energy evaluations or geometry optimizations
Operates on ligands alone or ligands posed in a protein active site
Can include the effects of solvation within 2 continuum dielectric approximations
Has multiprocessor capability using MPI
Calculates important minima in the unbound aqueous ensemble of a ligand
Provides the free energy of going from an ensemble of solution phase conformers to a single, bioactive conformation
Calculates the Hydration Free Energy of unbound ligands
Calculates the Strain Free Energy of any conformation of a ligand
As input, SZYBKI and Freeform will often take ligand conformer databases generated by OMEGA. For protein-ligand calculations, output from OEDocking is also often used as input for SZYBKI and Freeform. The output from these 2 programs is often directly actionable, or can be used as input for further physics-based modeling such as SZMAP.
The following utility programs are also included in this distribution:
OptLigandInDU: Optimizes a ligand in a rigid protein active site, suitable for large scale screening.
OptimizeDU: Optimizes a protein-ligand complex in a design unit, allowing the protein to be partially flexible, suitable for lead optimization.