PathFinder procedure

Figure 5.3. Schematic view of the Pathfinder procedure the frequency distribution is extracted from GRiD MiF, and is consequentiy encoded into a molecular fingerprint.

The molecular interaction fields (MIF) obtainable by GRID [1] may be used to define the solvent accessible surface, which resembles the molecular shape. However, MIFs are descriptors that depend on the 3D-location, and usually several thousand are required to describe a shape. In this chapter we present a novel procedure, called PathFinder, which encodes MIF into a compact alignment-free description of molecular shape. 

The absence of a precise shape description, based on the GRID molecular interaction fields, prompted the development of a new procedure, called PathFinder, that is described here. 

We have presented a netv procedure, called PathFinder, aimed at encoding the GRID molecular interaction fields into invariant shape-descriptors, suitable for similarity and complementarity issues. Shape similarity is the underlying foundation of ligand-based methods tvhile shape complementarity is the basis of many receptor-based designs. 

Stable-labeled isotopes — dicamba-d3, 2,4-D-d3, atrazine-d5, diazinon-djQ, and lindane-d — were synthesized by Pathfinder Laboratories, St. Louis, Missouri. Pentachlorophenol-l c was obtained from MSD-isotopes, Division of Merck Frost Canada Inc., Montreal, Canada. The deuterated compounds and the C-labeled pentachlorophenol were spiked into every sample at known concentration and were used to quantitate the naturally abundant compounds by stable-isotope dilution procedures (23-24). 

Plate 15 MIF transformation obtained with PathFinder program. Left, the transformation for the NAD site of the protein L-aspartate oxidase. Right, the MIF transformation for the NAD ligand molecule alone. The two maps are very similar, although the NAD molecule was roto-translated from the initial true position. The map comparison obtained from PathFinder can substitute virtual docking procedures. 

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