Molecular modelling hydrophobic bonding potential

Most commonly used is certainly the molecular electrostatic potential. It can be derived from any kind of charge distribution. Usually, the MEP is first calculated on a grid and subsequently transformed to the sphere or Gaussian representation. Quite important is the electron density distribution, which closely models the steric occupancy by a molecule. Other approaches utilize artificial fields for physicochemical properties commonly associated with binding, like a field for the hydrophobicity [193] or H-bonding potential [133,194]. 

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). 

In addition to the steric and electrostatic descriptors, it was proposed to use other 3D molecular fields characterized by the sampling over the rectangular grid - in particular, the hydrophobic field/molecular lipophilic potential (MLP), ° hydrogen bonding and quantum-chemical parameters, e.g., orbital densities.Descriptor selection techniques are often recommended to enhance the stability, predictivity and interpretability of the CoMFA models. ... 

Improvements of the Pohtzer hydrophobic model were later proposed using additional quantum-chemical descriptors derived from the molecular electrostatic potential, dipole moment, and ionization energies. These descriptors were searched for to give the best estimations of the cavity term, polarity/dipolarizability term, and hydrogen-bond parameters defined in -> linear solvation energy relationships [Haeberlein and Brinck, 1997]. 

The atomic partial charge of the model phase and hydrocarbon does not change significantly after optimization of the eomplex form, while the electron potential is slightly shifted toward the molecular interaction side. These results clearly indicate the existence of different retention mechanisms on graphitized carbon phases, a hydrophobic interaction and hydrogen bonding. 

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