Roughness of molecular property landscapes and its impact on modellability
Matteo Aldeghi, David E. Graff, Nathan Frey, Joseph A. Morrone, Edward O. Pyzer-Knapp, Kirk E. Jordan, Connor W. Coley
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Abstract
In molecular discovery and drug design, structure-property relationships and activity landscapes are often qualitatively or quantitatively analyzed to guide the navigation of chemical space. The roughness (or smoothness) of these molecular property landscapes is one of their most studied geometric attributes, as it can characterize the presence of activity cliffs, with rougher landscapes generally expected to pose tougher optimization challenges. Here, we introduce a general, quantitative measure for describing the roughness of molecular property landscapes. The proposed roughness index (ROGI) is loosely inspired by the concept of fractal dimension and strongly correlates with the out-of-sample error achieved by machine learning models on numerous regression tasks.