Szybki TK 1.7.0

New features

  • An extension of the MMFF94 force field for tricoordinate boron compounds is offered in this release. Most compounds containing B-X bonds where X=C,N,O,S, and H are covered with the following exceptions: X=N(imine),N(sulfonamide), N(pyridinium) and N(quaternary). Also not supported are compounds in which boron is bonded to X=F,Cl,Br,I,B and Si, or makes a bond angle BYX. Compounds in which boron is a part of four-membered rings of B1CCC1 type are also not available in the current parameterization because their existence is questionable: Ab initio calculations at the MP2/6-31G** level failed to identify stable structures for them (highly polar structures in which boron is four-coordinated are formed).

  • NOTE WELL: Because of the partial parameterization for boron-containing compounds, users of the OEMMFF class (derived from OEGenericFF) need to pay attention to the return value of the OEMolPotential::OEGenericFF::Setup method: In the case where the parameters for a specific boron molecule are not available, this function returns false. Checking the return value of OEMolPotential::OEGenericFF::PrepMol is not enough, because it does not catch the case of missing force field parameters for a specific compound.

  • Two new API methods have been added which control the salt concentration for all PB calculations with Szybki TK. These are: SetSaltConcentration and GetSaltConcentration. The first method takes salt concentration in M as a float number. The valid range is 0 - 0.08M; this method should not be used for higher salt concentrations. The second method returns the current salt concentration as a float. Default value is zero. Previous versions of Szybki TK assumed zero salt concentration.

  • All PB calculations carried out with the previous Szybki TK versions used Bondi atomic radii. The current release offers two additional sets of atomic radii, called ZAP7 and ZAP9 as alternatives. They are described by Nicholls et. al. The new method: SetAtomicRadii allows the use of one of these two sets. The new method GetAtomicRadiiType returns the type of current atomic radii set.

  • Better control of dielectric constants is provided. This includes a new method: SetSolventDielectric which allows change from the default value of 80. Method GetSolventDielectric returns the current value of the solvent dielectric constant. Method: SetSolventModel which determines the solvation model for a free ligand in solution, now takes an additional default parameter which sets the intrinsic dielectric constant of the ligand.

  • A method which obtains gradients from the single point calculations is added. Specifically, a new method OESzybkiResults.GetGradients is added to the szybki_results.h header, and two new methods to the szybki.h header file. There are: SetCalculateGradients and GetCalculateGradients.

  • Enforcement of proper behavior by the OESzybki.operator() for molecules without 3D coordinates. Such molecules are not processed and a warning is issued.

Bug fixes

  • Method GetProteinBoundLigandEntropy is protected from selection of an inappropriate protein-ligand electrostatic model (entropy calculations for protein-bound ligands are done with the OEProteinElectrostatics.ExactCoulomb model).

  • Calling SetRunType with an argument OERunType.CartesiansOpt immediately after a call to same method but with an argument OERunType.TorsionsOpt caused missing potential values for bonds and bond angles. The problem is fixed.

  • Method OESzybkiResults.Print was not reporting MMFF terms in the case when OESzybki.SetProtein was used. The bug is fixed. Also, some minor improvements to this method is made, so it is clear which terms contribute to the total protein-ligand interactions and which are reported only for comparison. For example the usage of OEProteinElectrostatics results in reporting the exact and approximated Coulomb terms, however only the latter is used in the reported protein-ligand interaction.

  • Fixed a minor bug where unnecessary warnings regarding missing protein parameters were issued in an entropy calculation where the protein is held rigid. This happens when mistakes or inaccuracies in the input protein structures lead to undefined force field parameters.

  • Previously, processed molecules were output with aromaticity specified according to the MMFF94 aromaticity model. Now, output molecule are converted to the OE aromaticity model.

  • Entropy calculations using the quasi-Newton method now give significantly more accurate answers in the two extreme cases where the input ligand structure is a) already optimized, or b) has a very high-energy (i.e. poor) structure.