3.2 Theory

Pkatyper enumerates charge states based on primary, secondary and tertiary atom types of each atom in a molecule. The primary atom type is based on the atom's group and its valence. The primary atom-type defines the atom's basic propensity to support a formal charge. The secondary atom-type is defined by the atom-type of the neighbors or each atom. These secondary atom-types, such as aromaticity, alpha-beta unsaturation, or electronegative-groups, modulate each atom's basic propensity to support formal charges. The tertiary atom-types assess the effects of nearby formal charges on a given atom's formal charge. The combination of the primary, secondary and tertiary atom-types determine which formal charge states are allowed for each atom in a molecule. The primary and secondary atom-types are determined once, while the tertiary atom-types are determined as part of the enumeration process.

Pkatyper is a rudimentary approach to pKa prediction. While pkatyper is not suited for prediction of absolute pKas, it is quite amenable to enumeration of all reasonable charge states of a very wide variety of small-molecule chemistries.

Pkatyper is not a conformer generation program and will not create coordinates for molecules that are read in coordinateless. When used on molecules with three-dimensional coordinates, pkatyper attempts to place new hydrogens in a reasonable manner. However, pkatyper does not modify the heavy-atom coordinates of the molecule. In cases where the change in protonation-state dictates a change in conformation, one will need to use a conformer-generation tool (such as Omega) to generate reasonable conformations from the output from pkatyper. We recommend that in preparation of small-molecules for study, charge-state and tautomer enumeration be performed before conformer generation.

In the future, OpenEye will release a product which assigns a pKa value to each of the enumerated states.

				QuacPac Quality Atomic Charges, Proton Assignment and Canonicalization