Molecular Descriptors, Structure Generation, and Inverse QSAR/QSPR Based on SELFIES.

For inverse QSAR/QSPR in conventional molecular design, several chemical structures must be generated and their molecular descriptors must be calculated. However, there is no one-to-one correspondence between the generated chemical structures and molecular descriptors. In this paper, molecular descriptors, structure generation, and inverse QSAR/QSPR based on self-referencing embedded strings (SELFIES), a 100% robust molecular string representation, are proposed. A one-hot vector is converted from SELFIES to SELFIES descriptors x , and an inverse analysis of the QSAR/QSPR model y = f ( x ) with the objective variable y and molecular descriptor x is conducted. Thus, x values that achieve a target y value are obtained. Based on these values, SELFIES strings or molecules are generated, meaning that inverse QSAR/QSPR is performed successfully. The SELFIES descriptors and SELFIES-based structure generation are verified using datasets of actual compounds. The successful construction of SELFIES-descriptor-based QSAR/QSPR models with predictive abilities comparable to those of models based on other fingerprints is confirmed. A large number of molecules with one-to-one relationships with the values of the SELFIES descriptors are generated. Furthermore, as a case study of inverse QSAR/QSPR, molecules with target y values are generated successfully. The Python code for the proposed method is available at https://github.com/hkaneko1985/dcekit.