Table 3.
Top 13 Physicochemical and Molecular Descriptor Parameters That Correlate with the Fraction Unbound in the Caseum Surrogatea
| parameter | description | binning of parameter | correlation | 2D distance score |
|---|---|---|---|---|
| AromRings | aromatic rings | molecular shape character | − | 0.022 |
| Mol_Sol | molecular solubility | solubility | + | 0.036 |
| sp2 | sp2 carbon count | molecular shape character | − | 0.046 |
| D1 | hydrophobic volume | lipophilicity | − | 0.049 |
| IW1 | hydrophilicity/lipophilicity unbalance | lipophilicity | + | 0.061 |
| ID1 | hydrophilicity/lipophilicity unbalance | lipophilicity | + | 0.061 |
| Ring_count | ring count | molecular shape character | − | 0.066 |
| R | volume/surface ratio | molecular shape character | − | 0.068 |
| Logp_nOct | logP | lipophilicity | − | 0.068 |
| PB | plasma protein binding | plasma protein binding | − | 0.068 |
| CW2 | hydrophilic volume per surface unit | lipophilicity | + | 0.074 |
| HAS | hydrophobic surface area | lipophilicity | − | 0.075 |
| LogD | logD | lipophilicity | − | 0.076 |
a
The ranking of all correlations is based on the p1 and p2 PCA loading. The correlation is quantified by the distance between fu surrogate experimental data and the descriptor in the p1/p2 space (i.e., the shorter the distance, the greater the correlation). Positive correlations (i.e., fu increases with an increase in the parameter) and negative correlations (i.e., fu decreases with an increase in the parameter) are indicated by + and −, respectively.