Overview

SZYBKI consists of four 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, a protein) with plausible 3-dimensional atomic coordinates. The other program, Freeform, calculates some thermodynamic properties for small molecules that are useful for drug discovery. 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.

Note

Units of energy in various SZYBKI outputs are in kcal/mol.

Applications

The SZYBKI distribution comprises two applications:

SZYBKI

  • 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 two continuum dielectric approximations

  • Has multiprocessor capability using MPI

Freeform

  • 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 two programs is often directly actionable, or it can be used as input for further physics-based modeling such as SZMAP.

Utility Programs

The following utility programs are also included in this distribution:

  • OptLigandInDU: Optimizes a ligand in a rigid protein active site, making it suitable for large scale screening.

  • OptimizeDU: Optimizes a protein-ligand complex in a design unit, allowing the protein to be partially flexible, making it suitable for lead optimization.