In a database of about 2000 approved drugs, represented by 105 structural conformers,
we have performed 2D comparisons (Tanimoto coefficients) and 3D superpositions. For one class of drugs the correlation
between structural resemblance and similar action was analysed in detail.
In general Tanimoto cofficients and 3D scores give similar results, but we
find that 2D similarity measures neglect important structural/funtional
features. Examples for both over- and underestimation of similarity by
2D metrics are discussed. The required additional effort for 3D superpositions
is assessed by implementation of a fast algorithm with a processing
time below 0:01 seconds and a more sophisticated approach (0:5 seconds
per superposition). According to the improvement of similarity detection
compared to 2D screening and the pleasant rapidity on a desktop PC,
full{atom 3D superposition will be an upcoming method of choice for
library prioritization or similarity screening approaches.
We show that it is not possible to approximate the minimum Steiner tree problem within 1+1/162 unless RP=NP. The currently best known lower bound is 1+ 1/400. The reduction is from Hastad’s nonapproximability result for maximum satisfiability of linear equation modulo 2. The improvement on the nonapproximability ratio is mainly based on the fact that our reduction does not use variable gadgets. This idea was introduced by Papadimitriou and Vempala.