Ak. Ghose et al., PREDICTION OF HYDROPHOBIC (LIPOPHILIC) PROPERTIES OF SMALL ORGANIC-MOLECULES USING FRAGMENTAL METHODS - AN ANALYSIS OF ALOGP AND CLOGP METHODS, The journal of physical chemistry. A, Molecules, spectroscopy, kinetics, environment, & general theory, 102(21), 1998, pp. 3762-3772
Molecular hydrophobicity (lipophilicity), usually quantified as log P
(the logarithm of 1-octanol/water partition coefficient), is an import
ant molecular characteristic in drug discovery. ALOGP and CLOGP are tw
o of the most widely used methods for the estimation of log P. This wo
rk describes an extensive reparametrization of the atomic log P values
and a detailed comparison of the performance of ALOGP and CLOGP metho
ds on the Pomona Medchem database. Only the ''star list'' compounds ha
ving precisely measured log P values were used in this analysis. While
the overall results with both methods are similar, analysis shows tha
t the CLOGP method is better for very small molecules in the range of
1-20 atoms. The two methods are almost comparable in the range of 21-4
5 atoms, while the ALOGP method has better accuracy for molecules with
more than 45 atoms. Although the rms deviation and the correlation co
efficient for CLOGP predictions were marginally better than those for
corresponding ALOGP predictions, the latter showed a very stable perfo
rmance for all classes of organic compounds analyzed. The ALOGP method
can be used to compute estimates of most neutral organic compounds ha
ving C, H, O, N, S, Se, P, B, Si, and halogens. It also covers most zw
itterionic compounds having amine and carboxylic acids and ammonium ha
lide salts. The CLOGP method has improved considerably over the years
to cover most neutral organic compounds, but it still has some undefin
ed fragments. Finally, unlike CLOGP and other methods of predicting li
pophilicity, the ALOGP method has multiple uses, such as the estimatio
n of local hydrophobicity, the visualization of molecular hydrophobici
ty maps, and the evaluation of hydrophobic interactions in protein-lig
and complexes.