Diverse Hits in De Novo Molecule Design: Diversity-Based Comparison of Goal-Directed Generators

P Renz, S Luukkonen, G Klambauer - Journal of Chemical …, 2024 - ACS Publications
Journal of Chemical Information and Modeling, 2024ACS Publications
Since the rise of generative AI models, many goal-directed molecule generators have been
proposed as tools for discovering novel drug candidates. However, molecule generators
often produce highly similar molecules and tend to overemphasize conformity to an
imperfect scoring function rather than capturing the true underlying properties sought. We
rectify these two shortcomings by offering diversity-based evaluations using the# Circles
metric and considering constraints on scoring function calls or computation time. Our …
Since the rise of generative AI models, many goal-directed molecule generators have been proposed as tools for discovering novel drug candidates. However, molecule generators often produce highly similar molecules and tend to overemphasize conformity to an imperfect scoring function rather than capturing the true underlying properties sought. We rectify these two shortcomings by offering diversity-based evaluations using the #Circles metric and considering constraints on scoring function calls or computation time. Our findings highlight the superior performance of SMILES-based autoregressive models in generating diverse sets of desired molecules compared to graph-based models or genetic algorithms.
ACS Publications
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