Software → ROx

Many recent studies have compared shape-matching to docking as virtual screening tools ([1], [4], [3]). The general consensus among many of these studies is that docking tools do not address, in adequate detail, the affinity of molecules when compared to a query molecule or a pharmacaphore. The use of shape-based, ligand-oriented methods was therefore justified as an alternative method to determine this functionality. Most high-throughput shape-based screening platforms are based on the premise that molecules have similar shape if their volumes overlay well, and that a volume mismatch is more a indication of shape dissimilarity.

ROx is InhibOx’s in-house molecule shape comparison platform. ROx has been implemented in an efficient manner to enable the screening of many millions of molecules, represented in 3-D conformational databases, in a reasonable amount of time. ROx searches for molecules with similar shapes by comparing volume overlaps having aligned them onto a common coordinate frame.

ROx uses a customised simplex optimiser based method to align database molecules against the query molecule and then assigns scores for their similarity [5] using the Tanimoto(Eq. (1 )) and Carbo (Eq. (2 )) measures. A good review of similarity measures currently in use can be found in the paper by Raymond and Willett [2].

(1)

(2)

References