Multiple linear regression models for predicting the n‑octanol/water partition coefficients in the SAMPL7 blind challenge

Lopez, Kenneth; Pinheiro, Silvana; Zamora, William J.

A multiple linear regression model called MLR-3 is used for predicting the experimental n-octanol/water partition coefficient (log P(N)) of 22 N-sulfonamides proposed by the organizers of the SAMPL7 blind challenge. The MLR-3 method was trained with 82 molecules including drug-like sulfonamides and small organic molecules, which resembled the main functional groups present in the challenge dataset. Our model, submitted as “TFE-MLR”, presented a root-mean-square error of 0.58 and mean absolute error of 0.41 in log P units, accomplishing the highest accuracy, among empirical methods and also in all submissions based on the ranked ones. Overall, the results support the appropriateness of multiple linear regression approach MLR-3 for computing the n-octanol/water partition coefficient in sulfonamide-bearing compounds. In this context, the outstanding performance of empirical methodologies, where 75% of the ranked submissions achieved root-mean-square errors < 1 log P units, support the suitability of these strategies for obtaining accurate and fast predictions of physicochemical properties as partition coefficients of bioorganic compounds. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10822-021-00409-2.