New utility program called
FreeFormis 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
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
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
-optMethodis 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
-conjis 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
-optGeometryis introduced for selection of coordinate system to be used during optimization. It replaces no longer supported options
-no_opt. It can be also used to optimize hydrogen atoms positions only, instead of using for that purpose
Molecules from the input file which failed during processing are by default written to the separate molecular file. See the description of new option
Starting from this release flags
-harm_smartsare 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.
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_complexwere used, had attached a protein molecule. This bug was fixed in the current release.