Quantized surface complementarity diversity (QSCD): a model based on small molecule-target complementarity.

A model of molecular diversity is presented. The model, termed "Quantized Surface Complementarity Diversity" (QSCD), defines molecular diversity by measuring molecular complementarity to a fully enumerated set of theoretical target surfaces. Molecular diversity space is defined as the molecular complement to this set of enumerated surfaces. Using a set of known test compounds, the model is shown to be biologically relevant, consistently scoring known actives as similar. At the resolution of the model, which examines molecules "quantized" into 4.24 A cubic units and treats four points of specific energetic complementarity, the minimum number of compounds needed to fully cover molecular diversity space up to volume 1070 cubic A is estimated to be on the order of 24 million molecules. Most importantly, QSCD allows for individual points in diversity space to be filled by direct modeling of molecular libraries into detailed 3D templates of shape and functionality.