2. Theory

EON uses a field-based measure of Tanimoto to compare the electrostatic potential of two small molecules. This electrostatic potential is calculated internally using Zap, OpenEye's Poisson-Boltzman (PB) electrostatics toolkit.

The basic equation for a field Tanimoto is:

$\begin{displaymath} Tanimoto_{A,B} = \frac{\int A(\vec{r})*B(\vec{r})} {\int A(... ...}) + \int B(\vec{r})*B(\vec{r}) - \int A(\vec{r})*B(\vec{r})} \end{displaymath}$

(2.1)

The two boundary cases for Electrostatic Tanimoto occur when :

$\begin{eqnarray*} Tanimoto & = &\frac{\int A(\vec{r})*A(\vec{r})} {\int A(\vec{... ...A(\vec{r})*A(\vec{r}) - \int A(\vec{r})*A(\vec{r})} \\ & = & 1 \end{eqnarray*}$

and the opposite case, when :

$\begin{eqnarray*} Tanimoto & = &\frac{\int A(\vec{r})*-A(\vec{r})} {\int A(\vec... ...A(\vec{r}) + \int A(\vec{r})*A(\vec{r})} \\ & = & -\frac{1}{3} \end{eqnarray*}$

In EON, we report two different Electrostatic Tanimoto(ET) measures, based on the outer dielectric used in the PB calculation. ET_pb uses an outer dielectric of 80, while ET_coul uses a value of 2.0. The rational for using a PB electrostatic field is that the external potential is dampened by orientation of the aqueous solvent. It is a common observation that proteins essentially act to reproduce the aqueous desolvation of well-bound ligands. As a result a PB electrostatic field is more likely to correctly capture the essential elements of binding than that from the Coulombic field. However, this would still seem to be a point to be proven. As such we provide both Tanimotos. They typically track each other very closely.

For hit list ranking, we also report a score (ET_combo) that is the sum of the Shape Tanimoto (ST) and the PB Electrostatic Tanimoto (ET_pb).