High-throughput Screen vHTS and Protein Selectivity

Virtual High-throughput Screen (vHTS) and Protein Selectivity 

The Fingerprint-based Lead Identification Protocol (FLIP) [23] uses the information about the known or potential active site of a protein to data mine compound collections to select compounds that are likely to bind to the defined active site. 

The three features FI, F2 and F3 from a molecule form a triangle and the three sides of this triangle are dl (F1-F2), d2 (F2-F3) and tJ3 (F1-F3) with d3 d2 dl. This information is mapped on to a grid. First FI is placed at the origin (0,0) since it is the feature at which the minimal and maximal feature distances meet. F2 is the feature of minimal distance from feature FI and lies on the X-axis (0,A). Once the coordinates of FI and F2 have been assigned, it is easy to extrapolate the coordinates for F3 (B,C). This is represented by the phar-macophoric index P=F (F1,F2,F3,A,B,C). 

The 3D fingerprint for the receptor is compared against the 3D fingerprint for each molecule in the Catalyst database to select the top percentage of hits. There are two possible ways of comparing 3D fingerprints  

Compute similarity coefficients (Tanimoto, Dice, Ochia, Hamming) between the active site fingerprint and the fingerprint for each molecule in the Catalyst database. The top N% of compounds can be selected by ranking the compound collection in descending order based on the similarity coefficient. 

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