Electrostatic potential hydrogen bonding

The representation of molecules by molecular surface properties was introduced in Section 2.10. Different properties such as the electrostatic potential, hydrogen bonding potential, or hydrophobicity potential can be mapped to this surface and seiwe for shape analysis [44] or the calculation of surface autocorrelation vectors (refer to Section 8.4.2). 

The descriptors of the molecular structures that are used in QSAR include physical and electronic properties, fragment compositions, as well as calculated properties of the three-dimensional (3D) structures of the compounds. The 3D properties include scalar parameters like solvent-accessible surface area, or hydro-phobic surface area. They also include field-type reductions of the structure that represent steric interactions, electrostatic potentials, hydrogen-bonding potential, hydrophobic interactions, and so on. 

The first three terms, stretch, bend and torsion, are common to most force fields although their explicit form may vary. The nonbonded terms may be further divided into contributions from Van der Waals (VdW), electrostatic and hydrogen-bond interactions. Most force fields include potential functions for the first two interaction types (Lennard-Jones type or Buckingham type functions for VdW interactions and charge-charge or dipole-dipole terms for the electrostatic interactions). Explicit hydrogen-bond functions are less common and such interactions are often modeled by the VdW expression with special parameters for the atoms which participate in the hydrogen bond (see below). 

These studies are continuing to evaluate the effects of different potential functions, contributions from electrostatic and hydrogen bond attractions, ten erature, etc. The effects of solvents, complexing agents, and adjacent surfaces of crystalline regions will be investigated in due course. 

Molecules are characterized by potential hydrogen bonding, polar, hydrophobic, and electrostatic interactions in 3D space, using 3D molecular fields. Techniques such as Comparative Molecular Field Analysis (CoMFA), which considers the 3D distribution of electrostatic and steric fields, have been applied to congeneric series of enzyme substrates or inhibitors generating 3D QSAR equations. Most examples of such applications are to modeling CYP substrate and inhibitor specificity and these have been extensively reviewed in the literature (Ekins et al., 2000 2001 Ter Laak and Vermeulen, 2001 Ter Laak et al., 2002). 

At this point in the design procedure, the molecules that have been found fit the site in a geometric sense but do not necessarily match in detailed chemistry. Electrostatic and hydrogen bonding features of the receptor are now examined. In this calculation, each atom of the small molecule is used to define a location at which the electrostatic potential from the protein atoms is evaluated (Equation 2). 

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