HINT, hydrophobic fields

HINT adjunct to CoMEA, computes hydrophobic fields EduSoft, Inc. (KeHog/Abraham)... 

D. J. HINT a new method of empirical hydrophobic field calculation for CoMFA J. Comput.-Aided Mol. Des. 1991, 5, 454—552. 

HINT), is a hydrophobic field calculated by -> Leo-Hansch hydrophobic fragmental constants scaled by surface area and a distance-dependent function [Kellogg et al., 1991 Kellogg and Abraham, 1992a Abraham and Kellogg, 1993]. Hydropathy is a term used in structural molecular biology to represent the hydrophobicity of amino acid side chains. 

HINT = Hydropatic INTeractions molecular interaction fields ( hydrophobic fields)... 

Other fields than those implemented in the CoMFA program have been proposed for 3D QSAR analyses, e.g. different interaction fields calculated by the program GRID [33, 909, 910] or hydrophobic fields derived from HINT [918 — 921] (chapter 9.2). In addition, any other parameters, e.g. physicochemical properties like log P or quantum-chemical indices, may be added to the X block, if they are properly... 

Two groups have developed hydrophobic fields for CoMFA 3D-QSAR applications. The HINT (hydrophobic interaction) program calculates the hydrophobic field of a molecule using Hansch-Leo hydrophobic constants scaled by surface area and a distance-dependent function. The MLP program... 

In addition or alternatively to these fields, hydrophobic fields, calculated e.g., by the program HINT, or GRID fields can be used. Arbitrary weights may be attributed to the different fields. An appropriate scaling of all variables has to be performed if additional properties, e.g., the lipophilicity parameter log P P = n-octanol/water partition coefficient), are included, to give a comparable weight to the individual fields and the single parameter(s). 

Here S is the solvent-accessible surface area for atom /, a, is the hydrophobic atom constant for atom /, and R , = e, where r is the distance between atom i and grid point t. In addition to supplementing standard CoMFA fields, HINT has been demonstrated to effectively model experimentally determined log P values in cases where CLOGP values fail. A different fragment-based, distance-dependent method to estimate lipophilicity, the molecular lipophilic potential (MLP), has been recently shown to be useful in docking and as a third field in CoMFA studies. 

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