A new forcefield for protein-ligand interactions has been added. It is a combination
of MMFF94S (or MMFF94) with Amber. In this combined force field, 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.
Two new methods were added to the API: OESzybki::SetTorsionConstraint
and OESzybki::ClearTorsionConstraint. The first one adds a
single-minimum harmonic torsional constraint for a torsion which is defined by
a SMARTS pattern. It uses the functional 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. The second method
removes the torsional constraint if it exists.
Estimation of ligand entropy using analytical MMFF Hessian is extended for
ligands bound in a rigid protein. Previously the entropy of only free ligands in
vacuum or in solution could be estimated with analytical second derivatives.
The method OESz::OESzybki::GetExactVdWProteinLigand was misspelled
(GetExactVdEProteinLigand instead of GetExactVdWProteinLigand).
When preoptimized ligands are used for entropy estimation it is necessary to gently
move the ligand out of the minimum. The gradient normal below which such a perturbation was
done was raised from 1 kcal/(mol Å\(\AA\)) to 10 kcal/(mol Å\(\AA\)).
Research showed that for some conformations the above limit was too low which resulted
in overestimation of its vibrational entropy.