Dataset Information

Inverse design of 3d molecular structures with conditional generative neural networks.

ABSTRACT: The rational design of molecules with desired properties is a long-standing challenge in chemistry. Generative neural networks have emerged as a powerful approach to sample novel molecules from a learned distribution. Here, we propose a conditional generative neural network for 3d molecular structures with specified chemical and structural properties. This approach is agnostic to chemical bonding and enables targeted sampling of novel molecules from conditional distributions, even in domains where reference calculations are sparse. We demonstrate the utility of our method for inverse design by generating molecules with specified motifs or composition, discovering particularly stable molecules, and jointly targeting multiple electronic properties beyond the training regime.

SUBMITTER: Gebauer NWA

PROVIDER: S-EPMC8861047 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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Inverse design of 3d molecular structures with conditional generative neural networks.

Gebauer Niklas W A NWA Gastegger Michael M Hessmann Stefaan S P SSP Müller Klaus-Robert KR Schütt Kristof T KT

Nature communications 20220221 1

The rational design of molecules with desired properties is a long-standing challenge in chemistry. Generative neural networks have emerged as a powerful approach to sample novel molecules from a learned distribution. Here, we propose a conditional generative neural network for 3d molecular structures with specified chemical and structural properties. This approach is agnostic to chemical bonding and enables targeted sampling of novel molecules from conditional distributions, even in domains whe ...[more]

PMID: 35190542

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Project description:Although massive data is quickly accumulating on protein sequence and structure, there is a small and limited number of protein architectural types (or structural folds). This study is addressing the following question: how well could one reveal underlying sequence-structure relationships and design protein sequences for an arbitrary, potentially novel, structural fold? In response to the question, we have developed novel deep generative models, namely, semisupervised gcWGAN (guided, conditional, Wasserstein Generative Adversarial Networks). To overcome training difficulties and improve design qualities, we build our models on conditional Wasserstein GAN (WGAN) that uses Wasserstein distance in the loss function. Our major contributions include (1) constructing a low-dimensional and generalizable representation of the fold space for the conditional input, (2) developing an ultrafast sequence-to-fold predictor (or oracle) and incorporating its feedback into WGAN as a loss to guide model training, and (3) exploiting sequence data with and without paired structures to enable a semisupervised training strategy. Assessed by the oracle over 100 novel folds not in the training set, gcWGAN generates more successful designs and covers 3.5 times more target folds compared to a competing data-driven method (cVAE). Assessed by sequence- and structure-based predictors, gcWGAN designs are physically and biologically sound. Assessed by a structure predictor over representative novel folds, including one not even part of basis folds, gcWGAN designs have comparable or better fold accuracy yet much more sequence diversity and novelty than cVAE. The ultrafast data-driven model is further shown to boost the success of a principle-driven de novo method (RosettaDesign), through generating design seeds and tailoring design space. In conclusion, gcWGAN explores uncharted sequence space to design proteins by learning generalizable principles from current sequence-structure data. Data, source codes, and trained models are available at https://github.com/Shen-Lab/gcWGAN.

Dataset Information

Inverse design of 3d molecular structures with conditional generative neural networks.

Publications

Inverse design of 3d molecular structures with conditional generative neural networks.

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