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Molecular representations are of fundamental importance for the modeling and analysing molecular systems. The successes in drug design and materials discovery have been greatly contributed by molecular representation models. In this paper, we present a computational framework for molecular representation that is mathematically rigorous and based on the persistent Dirac operator. The properties of the discrete weighted and unweighted Dirac matrix are systematically discussed, and the biological meanings of both homological and non-homological eigenvectors are studied. We also evaluate the impact of various weighting schemes on the weighted Dirac matrix. Additionally, a set of physical persistent attributes that characterize the persistence and variation of spectrum properties of Dirac matrices during a filtration process is proposed to be molecular fingerprints. Our persistent attributes are used to classify molecular configurations of nine different types of organic-inorganic halide perovskites. The combination of persistent attributes with gradient boosting tree model has achieved great success in molecular solvation free energy prediction. The results show that our model is effective in characterizing the molecular structures, demonstrating the power of our molecular representation and featurization approach. [ABSTRACT FROM AUTHOR]

Artificial intelligence (AI) techniques have already been gradually applied to the entire drug design process, from target discovery, lead discovery, lead optimization and preclinical development to the final three phases of clinical trials. Currently, one of the central challenges for AI-based drug design is molecular featurization, which is to identify or design appropriate molecular descriptors or fingerprints. Efficient and transferable molecular descriptors are key to the success of all AI-based drug design models. Here we propose Forman persistent Ricci curvature (FPRC)-based molecular featurization and feature engineering, for the first time. Molecular structures and interactions are modeled as simplicial complexes, which are generalization of graphs to their higher dimensional counterparts. Further, a multiscale representation is achieved through a filtration process, during which a series of nested simplicial complexes at different scales are generated. Forman Ricci curvatures (FRCs) are calculated on the series of simplicial complexes, and the persistence and variation of FRCs during the filtration process is defined as FPRC. Moreover, persistent attributes, which are FPRC-based functions and properties, are employed as molecular descriptors, and combined with machine learning models, in particular, gradient boosting tree (GBT). Our FPRC-GBT models are extensively trained and tested on three most commonly-used datasets, including PDBbind-2007, PDBbind-2013 and PDBbind-2016. It has been found that our results are better than the ones from machine learning models with traditional molecular descriptors. [ABSTRACT FROM AUTHOR]