SZYBKI 1.8.0

New features

  • New utility program called FreeForm is available for Szybki users. It provides two distinct functionalities: evaluation of the solvation free energy of the input molecules and free energies of solution conformations.

  • A new forcefield for protein-ligand interactions is available upon selecting a new option -ff followed by Amber_MMFF94 or Amber_MMFF94S. It is a combination of MMFF94 (or MMFF94S) with Amber. In this combined force field, MMFF94 (or MMFF94S) is used to describe the intramolecular interactions of the ligand and the Amber force field is used for the VdW and Coulomb interactions between ligand and protein. Currently, this force field can be used only for ligands inside rigid proteins.

  • Entropy estimation based on analytical MMFF Hessian is extended for ligands bound in a rigid protein using the option -entropy.

  • Constraining torsion potential in the form: \(V=k_c(cos(phi) - cos(phi0))^2\), where \(k_c\) is the user specified force constant and \(phi0\) is the reference torsion dihedral angle is available with the use of the input flag -tor_constr.

  • New option -optMethod is introduced for optimization method selection. The possible choices of optimizers type are BFGS, conjugate gradient, steepest descent and mixtures of steepest descent preoptimization followed by BFGS of conjugate gradient. Option -conj is no longer supported.

  • Optimization of molecular systems with large number of degrees of freedom (>= 500) is by default done with the conjugate gradient method unless specifically requested with the option -optMethod.

  • New option -optGeometry is introduced for selection of coordinate system to be used during optimization. It replaces no longer supported options -opt_cart`, -opt_torsions, -solid and -no_opt. It can be also used to optimize hydrogen atoms positions only, instead of using for that purpose -fix_smarts.

  • Molecules from the input file which failed during processing are by default written to the separate molecular file. See the description of new option -keepFailures.

  • Starting from this release flags -fix_smarts and -harm_smarts are followed by the name of the text file containing a single line with a SMARTS pattern used to fix or constrain atoms. Input of SMARTS strings on the command line for those flags are not used anymore because some SMARTS strings may contain special characters which may be interpreted incorrectly on some platforms.

Bug fixes

  • A few numerical errors in the calculation of analytical second derivatives (Hessian matrix) in MMFF torsion and out-of plane terms have been fixed.

  • When preoptimized ligands are used for entropy estimation it is necessary to gently moved the ligand out of minimum. The gradient norm below which such a perturbation was done was raised from 1 kcal/(mol Å\(\AA\)) to 10 kcal/(mol Å\(\AA\)). Our research showed that for some conformations the above limit was too low which resulted in overestimation of its vibrational entropy.

  • The usage of AM1BCC charges for PB, Sheffield and Coulomb protein-ligand interactions (option -am1bcc) produces the output molecule which preserves the existing partial charges from the input molecule. In previous versions MMFF94 charges were attached to the output molecule.

  • Output ligand molecule in the oeb format in a run when protein was partially flexible and when a flags -out_protein or -out_complex were used, had attached a protein molecule. This bug was fixed in the current release.

Other changes

  • PVM (parallel virtual machine) is no longer supported. OpenMPI version 1.6 is supported on all platforms. The -mpi_np and -mpi_hostfile flags are now used to run SZYBKI in MPI mode. These new flags replace the oempirun script.

  • This will be the last release to support SuSe 10.