Selectivity GRID molecular interaction fields

The interaction of drug molecules with biological membranes is a three-dimensional (3D) recognition that is mediated by surface properties such as shape, Van der Waals forces, electrostatics, hydrogen bonding, and hydrophobicity. Therefore, the GRID force field [5-7], which is able to calculate energetically favorable interaction sites around a molecule, was selected to produce 3D molecular interaction fields. 

The second section refers to pharmacodynamic aspects and contains chapters on Protein selectivity studies using GRID-MIE by Thomas Fox, The Complexity of Molecular Interaction Molecular Shape Fingerprint by PathFinder Approach by McLay, Hann, Carosati, Cruciani, and Baroni, Alignment-Independent Descip-tors from Molecular Interaction Fields by Manuel Pastor, FLAP 4-point pharma-... 

In - grid-based QSAR techniques, the energy value at each grid point p constitutes a molecular descriptor. For the selected -> molecular interaction fields (steric, hydrophobic, coulombic, etc.), the calculated value at each grid point p depends on the relative orientation of the compound with respect to the grid. As a consequence, the use of... 

Depending on the selected probe and the defined potential energy function, several molecular interaction fields can be calculated. The most common are steric fields and electrostatic fields, sometimes referred as CoMFA fields because originally implemented in CoMFA. Several interaction fields are actually calculated in the - GRID method. 

The molecular shape field (MSF) is constituted by values of the molecular interaction potential (MEP) of selected grid points that compose the molecular surface [Urbano-Cuadrado, Carbo et al., 2007]. 

D QSAR analyses based on similarity matrices offer a valuable new tool for the quantitative description of structure-activity relationships. Also hydrophobic fields and interaction fields with different probe atoms may be implemented, like in CoMFA studies. It is hoped that the preliminary results [1064, 1065] stimulate active research in this field to achieve further methodological improvements. Several CoMFA-inherent problems apparently do not arise in the molecular similarity matrices approach, e.g. the cut-off selection, a proper grid spacing, and the elimination of variables having low variance. 

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