GRID probe

GRID probe Catalyst feature GRID IEa) CiTest weight... 

A careful pretreatment is necessary to focus on the relevant variables. Often variables with low absolute values (<0.01 kcal moT ) and those with low standard deviations (<0.02-0.03kcal mol" ) are removed in order to eliminate noise. Autoscaling is not recommended, since all the data comes from the same source (GRID probe-target interaction energies) and all the data are expressed in the same units (kcalmof ). Thus, autoscaling might introduce noise in the model. 

The first study to investigate selectivity profiles using MIFs in connection with a chemometric analysis was published about 10 years ago [5]. There, the behavior of all 64 possible DNA triplets with respect to 31 GRID probes was studied with GRID/PCA. 

Figure 3.9. x-Variable distribution for the 10 grid probes in the P pocket after BUW. Blue dots indicate energies in thrombin, red dots in trypsin, and green dots in factor Xa. 

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.

The descriptors developed to characterize the substrate chemotypes are obtained from a mixture of molecular orbital calculations and GRID probe-pharmacophore recognition. Molecular orbital calculations to compute the substrate s electron density distribution are the first to be performed. All atom charges are determined using the AMI Hamiltonian. Then the computed charges are used to derive a 3D pharmacophore based on the molecular electrostatic potential (MEP) around the substrate molecules. 

Figure 12.5. All the substrate atoms are classified into GRID probe categories depending on their hydrophobic, hydrogen-bond donor or acceptor capabilities. Starting from a randomly chosen atom their distances in the space are then binned and transformed into clustered distances. One set of descriptors is computed for each atom type category hydrophobic, hydrogen-bond acceptor and...

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