28.2.2 The OpenEye Hydrogen Count Model

OpenEye's hydrogen count valence model is used by OEChem when neither hydrogen counts nor valence are specified. The typical uses are reading molecules from PDB or XYZ format files without explicit hydrogens. This functionality is invoked by OEAssignImplicitHydrogens, which must always be followed by a call to OEAssignFormalCharges. This valence model is unique in that it only partially updates hydrogen counts, assuming the unfilled valences will be corrected by OpenEye's charge valence model above. In MDL's model for example, a neutral sodium atom is assumed to have one implicit hydrogen, i.e. sodium hydride instead of sodium metal. In OpenEye's hydrogen count valence model, a disconnected sodium atom is assumed to be a sodium cation, [Na+]. When reading from PDB files, this is a very reasonable assumption.

Note that although the OpenEye hydrogen count valence model often sets charge and protonation states to physiological conditions, it is neither intended to be a pKa nor ionization state predictor. Instead, it is a normalization. Much like many registry system (and the MDL valence model) will convert C(=O)[O-] to C(=O)O for registration purposes, this valence model converts the opposite direction to C(=O)[O-].

Carbon is always assumed to be at least four valent, and therefore neutral.
Nitrogens that are conjugated (have double bonds, or have neighbors that have double bonds, in their Kekulé representations) are assumed at least three valent and neutral, whilst all other nitrogens are assumed to be (minimum) four valent, with a +1 formal charge.
Oxygens are assumed to be at least two valent and neutral, unless they have a single bond to an atom that is doubly bonded to oxygen, in which case its assumed to be one valent, with a -1 formal charge.
Sulfur is assumed to always be at least two valent.

All other elements are assumed to have no implicit hydrogens, and the formal charge as specified by the OpenEye charge model. This models all disconnected halogens as halide anions, and when disconnected the metals listed above as cations.

These rules are sufficient to reasonably protonate proteins read from PDB files. However, as described above, these rules are not intended to be a comprehensive rule-based pKa predictor. Users interested in predicting physiological ionization, and protonation/disassociation state enumeration should contact OpenEye Scientific Software about our tools for exactly this task.

				OEChem - C++ Theory Manual Version 1.3.1

				OEChem - C++ Theory Manual Version 1.3.1