Favorable binding sites, GRID

Program GRID works in very much the same way, but the objective is to obtain chemically specific information about the molecule. An electrostatic potential does not normally allow one to differentiate between favorable binding sites for a primary or a secondary or a tertiary amine cation, or tetramethyl ammonium or... 

Figure 1.7. The same helix when the whole side chain is allowed to move freely. GRID now detects a favorable binding site where the hydroxy group (red sphere) of a threonine side chain and the terminal NHj " group (blue sphere) of the lysine can both interact simultaneously with the probe. See text.

GRID (http //www.moldiscovery.com/soft grid.php) is a computational procedure for determining energetically favorable binding sites on molecules of known structure. It may be used to study individual molecules such as drugs, molecular arrays such as membranes or crystals, and macromolecules such as proteins, nucleic acids, glycoproteins or polysaccharides. Several different molecules can be processed one after the other. 

To calculate the substrate specificity of CPN, the GRID potential energy method [1] was used to determine energetically favorable binding sites (Fig. 7). This led to several suggestions for substrate specificity and possible peptide inhibitors. New dipeptide substrates were synthesized, and the results confirmed the predictions made from the calculations [106]. 

Figure 4.7. The complementaiy site points used for pharmacophore fingerprint calculations (lower right), together with the energetically favorable contours from 5 GRID probes on a FactorXa binding site.

Fig. 4. Molecular modeling of (-)-2l -THC ligands with different substitution in the C-1 side chain position using molecular mechanics/molecular dynamics. CB1/CB2 receptor-excluded volume map (redcontours and essential volume map (white grid for the C-1 subsite in zl -THC series. The red area represents the free space within the receptor region that accommodates high-affinity C-1 -substituted ligands, whereas, C-1 substituents falling within the white grid experience unfavorable or less favorable interactions at the binding site...

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