论文标题

使用财产评估的有效查询优化分子

Optimizing Molecules using Efficient Queries from Property Evaluations

论文作者

Hoffman, Samuel, Chenthamarakshan, Vijil, Wadhawan, Kahini, Chen, Pin-Yu, Das, Payel

论文摘要

基于机器学习的方法显示了具有更理想的特性优化现有分子的潜力,这是加速新化学发现的关键一步。在这里,我们提出了QMO,这是一种基于Query的分子优化框架,可利用分子自动编码器的潜在嵌入。 QMO在一组分子属性预测和评估指标的指导下,基于有效的查询改善了输入分子的所需特性。我们表明,在相似性约束下,QMO在基准任务中优于优化小有机分子的基准任务中的现有方法。我们还使用QMO在两个新的挑战性任务中证明了重大的财产改进,这些任务在现实世界发现问题中也很重要:(i)优化现有的潜在潜在SARS-COV-2主要蛋白酶蛋白酶抑制剂针对更高的结合亲和力; (ii)改善已知的抗菌肽对较低的毒性。 QMO的结果显示出与外部验证的高度一致性,提出了有效的手段,以促进设计约束的物质优化问题。

Machine learning based methods have shown potential for optimizing existing molecules with more desirable properties, a critical step towards accelerating new chemical discovery. Here we propose QMO, a generic query-based molecule optimization framework that exploits latent embeddings from a molecule autoencoder. QMO improves the desired properties of an input molecule based on efficient queries, guided by a set of molecular property predictions and evaluation metrics. We show that QMO outperforms existing methods in the benchmark tasks of optimizing small organic molecules for drug-likeness and solubility under similarity constraints. We also demonstrate significant property improvement using QMO on two new and challenging tasks that are also important in real-world discovery problems: (i) optimizing existing potential SARS-CoV-2 Main Protease inhibitors toward higher binding affinity; and (ii) improving known antimicrobial peptides towards lower toxicity. Results from QMO show high consistency with external validations, suggesting effective means to facilitate material optimization problems with design constraints.

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