ADME ALMOND

Einally, there is a fourth program which encapsulates GRIND descriptors named ALMOND. ALMOND theory is described in Chapter 6. What we will describe below refers to our involvement in utilizing the GRIND descriptors to model and understand various ADME and safety properties. 

I 9 Molecular Interaction Fields in ADME and Safety 9.3.1.3 ALMOND Descriptors... 

In addition to the VolSurf treatment of the GRID fields, the information from the MIF can also be transformed to obtain a pharmacophoric type of representation, which is useful in the modeling of metabolic stability, cytochrome inhibition or even the direct study of the ADME related proteins (Fig. 10.3). The Almond software [17] transforms the MIF into a distance-based representation of the molecule interaction. These parameters describe the geometry of the interaction and QSAR models can be derived where the interaction with a protein is essential. Detailed information on these descriptors is presented elsewhere in this book. 

VolSurfwas initially validated on oral absorption [16, 17] and blood-brain-barrier permeation [18] models (see belovi ). VolSurf has continued to be developed to improve in silico predictions for ADME properties, although its use has also been extended to receptor-based evaluation of binding affinity [19, 20], While other soft-ivare tools for ADME modeling are available (see, e.g., [21]), the MIF-based collection of sofhvare and models available from Molecular Discovery (MD) is both extensive and ivell validated by the private sector. Three programs from MD, VolSurf, MetaSite and Almond, are particularly suited for rapid evaluation of large compound sets [22] in connection ivith ADME/Tox related properties ... 

The GRID force field represents the basis for several software packages specifically developed for application to pharmacodynamic aspects of drug research, including the programs ALMOND, Pathfinder, and FLAP or, in the ADME field, the programs VolSurf and MetaSite. 

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