Calculation of hydrophobic parameters directly from three-dimensional structures using comparative molecular field analysis

Abstract

Capacity ratio (log k') values, which are a measure of hydrophobicity, were calculated directly from the three-dimensional structures of 17 furans and 54 triazines using the comparative molecular field analysis approach. The H2O probe and the GRID force field, including hydrogen-bond potentials, yielded excellent correlations with the log k' values. Moreover, the predicted values of log k' from 14 additional triazine analogs showed excellent agreement with log k' values reported in the literature. Similar results were obtained for the octanol-water partition coefficients (log P) of 17 furans.

Calculation of Molecular Lipophilicity: State-of-the-Art and Comparison of LogP Methods on more than 96,000 Compounds

“…One of the first studies to predict log P by using potential energy fields calculated using the GRID and CoMFA approaches was done by Kim,127 who investigated H+, CH 3 , and H 2 O probes and calculated the best models using the “hydrophobic probe” H 2 O for relatively small series (20 or less compounds each) of furans, carbamates, pyridines, and pyrazines. In a similar study Waller128 predicted a small series of 24 polyhalogenated compounds.…”

Use of molecular modeling, docking, and 3D-QSAR studies for the determination of the binding mode of benzofuran-3-yl-(indol-3-yl)maleimides as GSK-3β inhibitors

“…4 and 6 indicate some possible contributions of hydrophobic contribution of the substituents toward the observed pIC 50 values as in the classical QSAR discussed above. It was previously studied that the steric contribution of CoMFA may include the hydrophobic contribution 38–43. The present CoMSIA results indicate separate contributions from the hydrophobic contributions even though the steric contributions may include the hydrophobic contributions of the substituents as in the case of CoMFA.…”

Three‐Dimensional, Quantitative‐Structure‐Property‐Relationship Study of Aqueous Solubility for Phenylsulfonyl Carboxylates Using Comparative‐Molecular‐Field Analysis and Comparative‐Molecular‐Similarity‐Indices Analysis

“…The comparative‐molecular‐field‐analysis method (CoMFA) ( Cramer et al, 1988 ) meets these requirements. From its advent, CoMFA has been developed as one of the most powerful tools in three‐dimensional‐QSPR (3D‐QSPR) ( Costantino et al, 2000 ; Kim, 1995 ; Kim and Martin, 1991 ; Yoo and Cha, 1995 ). The CoMFA model tries to correlate the targeted properties of a series of molecules with the fundamental steric and electrostatic properties and does not require predetermined physicochemical parameters for the analysis.…”