Automatic Chemical Design Using a Data-Driven Continuous Representation of Molecules

被引:2344
作者
Gomez-Bombarelli, Rafael [1 ]
Wei, Jennifer N. [2 ]
Duvenaud, David [3 ]
Hernandez-Lobato, Jose Miguel [4 ]
Sanchez-Lengeling, Benjamin [2 ]
Sheberla, Dennis [2 ]
Aguilera-Iparraguirre, Jorge [1 ]
Hirzel, Timothy D. [1 ]
Adams, Ryan P. [5 ,6 ]
Aspuru-Guzik, Alan [2 ,7 ]
机构
[1] Kyulux North Amer Inc, 10 Post Off Sq,Suite 800, Boston, MA 02109 USA
[2] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA
[3] Univ Toronto, Dept Comp Sci, 6 Kings Coll Rd, Toronto, ON M5S 3H5, Canada
[4] Univ Cambridge, Dept Engn, Trumpington St, Cambridge CB2 1PZ, England
[5] Google Brain, Mountain View, CA USA
[6] Princeton Univ, Princeton, NJ 08544 USA
[7] Canadian Inst Adv Res CIFAR, Biol Inspired Solar Energy Program, Toronto, ON M5S 1M1, Canada
基金
美国国家科学基金会;
关键词
SPACE; LIBRARY;
D O I
10.1021/acscentsci.7b00572
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
We report a method to convert discrete representations of molecules to and from a multidimensional continuous representation. This model allows us to generate new molecules for efficient exploration and optimization through open-ended spaces of chemical compounds. A deep neural network was trained on hundreds of thousands of existing chemical structures to construct three coupled functions: an encoder, a decoder, and a predictor. The encoder converts the discrete representation of a molecule into a real-valued continuous vector, and the decoder converts these continuous vectors back to discrete molecular representations. The predictor estimates chemical properties from the latent continuous vector representation of the molecule. Continuous representations of molecules allow us to automatically generate novel chemical structures by performing simple operations in the latent space, such as decoding random vectors, perturbing known chemical structures, or interpolating between molecules. Continuous representations also allow the use of powerful gradient-based optimization to efficiently guide the search for optimized functional compounds. We demonstrate our method in the domain of drug-like molecules and also in a set of molecules with fewer that nine heavy atoms.
引用
收藏
页码:268 / 276
页数:9
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