The invention discloses an intelligent molecular design method based on a mathematical
programming method and skeleton-group
coupling. According to the
algorithm, a Beis-Murcko skeleton and a group fragment are taken as structural members, a potential skeleton subset is obtained through skeleton similarity retrieval, and a candidate structure space is constructed; on the basis, fragment selection and counting of candidate molecules are modeled as a mixed integer nonlinear
programming (MINLP) problem, and structural feasibility constraints, property threshold constraints and scores / probabilities output by a
deep learning model are uniformly introduced as target functions or constraint conditions. Meanwhile, an improved SMILES-based
structure generation mechanism is adopted in the
algorithm to establish consistency bridging between a fragment set and structure character
string representation in the solving process, a fragment feasible solution is generated in combination with a
decomposition solving strategy, and then structure representation generation and
nonlinear property / model evaluation screening are carried out. And finally, outputting a molecular structure which meets the constraint and is optimal or approximately optimal in target.