Use of the hydrogen bond potential function in a comparative molecular field analysis (CoMFA) on a set of benzodiazepines

Abstract

The results of the GRID-Comparative Molecular Field Analysis (CoMFA) were compared with those of the SYBYL-CoMFA in a study of benzodiazepines. The results demonstrate that the hydrogen bonding function using the GRID H2O probe in a CoMFA can successfully describe the hydrophobic effects of substituents without any bias or preconcept of their effects in the development.

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

“…The results presented here are in line with our experience with the hydrogen-bonding potential function in describing hydrophobic interactions in various biological QSARs [18][19][20][21][22][23][24]. These results render further support to the use of the H20 probe in describing hydrophobic interactions in 3D QSAR.…”

“…4 [6,71. log P = a log k' + b (2) log P = alog k' + bHA + cHD + d (3) log P = alog k' + bHA + cHD + dcy + e (4) In our previous study [15], we proposed that the comparative molecular field analysis (CoMFA) [16] method, 0920-654X/$ 6.00 + 1.00 © 1995 ESCOM Science Publishers B.V. using the H20 probe and the hydrogen-bond potential in GRID [17], can be used to describe the hydrophobic properties of organic molecules in quantitative structure activity relationship (QSAR) studies. Since then, a number of examples have been presented where such molecular fields reproduced the traditional QSAR hydrophobic parameter log P or rc in both linear and nonlinear relationships [18][19][20][21][22][23][24]. However, the previous studies have two limitations.…”

A new procedure for improving the predictiveness of CoMFA models and its application to a set of dihydrofolate reductase inhibitors

“…In order to investigate the sensitivity of the analyses to the magnitude of the calculated interaction energies [1,25], the lattice of the automatically defined region was shifted Table 2).…”

3D QSAR based on conceptual DFT molecular fields: Antituberculotic activity

“…CoMFA is still used very often as it does often give good working QSAR. Over the years, several workers have introduced several new types of fields, adding hydrophobic [9], hydrogen donor and hydrogen acceptor [10] or lipophilic [11] information to the model. Our interest lies mainly in the use of fields originating from so-called conceptual or chemical DFT [12].…”