A Pareto Algorithm for Efficient De Novo Design of Multi-functional Molecules [electronic resource]

• Ngôn ngữ: eng
• Ký hiệu phân loại: 504.5 [Unassigned]
• Thông tin xuất bản: Washington, D.C. : Oak Ridge, Tenn. : United States. Dept. of Energy. Office of Science ; Distributed by the Office of Scientific and Technical Information, U.S. Dept. of Energy, 2016
• Mô tả vật lý: Size: Article No. 1600044 : , digital, PDF file.
• Bộ sưu tập: Metadata
• ID: 260795
• Chủ đề: 1. 60 applied life sciences; 2. Computer science; 3. Drug design; 4. Et al; 5. Fgfr; 6. Mathematical & computational biology; 7. Osdas; 8. Pharmacology & pharmacy; 9. Receptors; 10. Vegfr; 11. Zeolites

Tóm tắt

Here, we have introduced a Pareto sorting algorithm into Synopsis, a de novo design program that generates synthesizable molecules with desirable properties. We give a detailed description of the algorithm and illustrate its working in 2 different de novo design settings: the design of putative dual and selective FGFR and VEGFR inhibitors, and the successful design of organic structure determining agents (OSDAs) for the synthesis of zeolites. We show that the introduction of Pareto sorting not only enables the simultaneous optimization of multiple properties but also greatly improves the performance of the algorithm to generate molecules with hard-to-meet constraints. This in turn allows us to suggest approaches to address the problem of false positive hits in de novo structure based drug design by introducing structural and physicochemical constraints in the designed molecules, and by forcing essential interactions between these molecules and their target receptor.