Szybki TK 1.8.3

New features

  • New forcefield for ligand-ligand and protein-ligand interactions has been added. It is a combination of MMFF94S (or MMFF94) with intermolecular potential called IEFF developed at OpenEye. In this combined force field, MMFF94S is used to describe the intramolecular interactions while IEFF which has 3 components (vdW, Coulomb and Fermi repulsion) handles intermolecular interactions. Coulomb terms in IEFF require precalculated and assigned atomic multipoles to ligand and protein molecules. This task can be achieved with two OpenEye codes called MOLQM and PROTQM. IEFF has been described in the following publication:

    N. Hamaguchi, L. Fusti-Molnar and S. Wlodek
    Force-field and quantum-mechanical binding study of selected SAMPL3 host-guest complexes
    J. Comput. Aided Mol. Des. Vol. 26, pp. 577-582, 2012

    Please contact if you are interested in testing this new forcefield.

  • New overloaded method OESzybki.SetTorsionConstraint has been added to the public API. It allows selectively constraining a specific torsion in the optimized molecule.

  • A set of flexible residues in ligand optimization with partially flexible protein is no longer restricted to the specified distance from the ligand. This goal has been achieved by the expansion of the OEProtFlex namespace for new constants which might be passed to the OESz::OESzybkiOptions::SetProteinFlexibilityType method, and the addition of the new method OESz::OESzybkiOptions::AddFlexibleResidue which can be used multiple times to make a set of residues flexible.

  • Added new virtual method OEOpt::OEFunc1::IsRedundant. It allows to check if two formally numerically different sets of coordinates indeed represent two different points in the coordinate space. This method has no trivial implementation in OEQuatAdaptor.IsRedundant.

  • MMFF calculations now allow for a “DUMMY” atom type, OEMMFFType.DUMMY to specify that an atom should be avoided during an MMFF energy calculation.

  • Added a DUMMY atom type to the AMBER force field to specify that an atom should be avoided during an AMBER energy calculation.

Major bug fixes

  • Fixed a rare crash when using the AMBER force field on some platforms.

  • A combination of Newton optimization with the use of the following two methods: OESz::OESzybkiOptions::SetProteinElectrostaticModel and OESz::OESzybkiOptions::SetExactVdWProteinLigand with parameters OEProteinElectrostatics.ExactCoulomb and true respectively caused that Coulomb potential was missing from the intermolecular interaction. That bug has been fixed.

  • OESzybkiResults.GetLnQvib and OESingleConfResult.GetLnQvibrational will no longer return negative infinity on Windows for large ligands.

Minor bug fixes

  • Fixed the name of the saved electrostatic grid file when the name of the molecule is used as part of the file name, by replacing all non alpha-numeric characters with an underscore character.

  • An attempt to use Newton optimization with a potential for which second derivatives are not implemented is terminated with a proper error message.

  • When AM1BCC charges are selected in Sheffield or PB solvation models for multiply charged species, SCF procedure in AM1 might not converge within 20 cycles (this has been observed for methotrexate only so far). To make sure that the electron density is converged, and calculated atomic charges stable, we allow up to 1000 SCF iterations for multiply charged molecules.

  • Return value of the method OESzybkiResults.GetTotalEnergy for protein-ligand system with partially flexible protein does not contain intrinsic MMFF energy of the protein.

  • An attempt to use protein flexibility type which is not a member of the OEProtFlex namespace in the method OESz::OESzybkiOptions::SetProteinFlexibilityType` issues an error message ``Unrecognized protein flexibility.

  • An error message generated upon the attempt of using partially flexible protein in solid body optimization type is generated instead of warning.

  • A more informative error message is generated upon the attempt of free ligand entropy estimation in the situation when protein environment is set.

  • An error message is generated when trying to use Newton optimization for protein-ligand systems with protein electrostatic models different than OEProteinElectrostatics.NoElectrostatics or OEProteinElectrostatics.ExactCoulomb

  • Flexible polar hydrogens are printed when residue polar hydrogens are asked to be optimized along with the ligand.

Documentation fixes

  • Documentation for the OEMolMMFF::OEMMFFSubsetVdw class has been removed.