title: Development of a New De Novo Design Algorithm for Exploring Chemical Space.
abstract: In the first stage of development of new drugs, various lead compounds with high activity are required. To design such compounds, we focus on chemical space defined by structural descriptors. New compounds close to areas where highly active compounds exist will show the same degree of activity. We have developed a new de novo design system to search a target area in chemical space. First, highly active compounds are manually selected as initial seeds. Then, the seeds are entered into our system, and structures slightly different from the seeds are generated and pooled. Next, seeds are selected from the new structure pool based on the distance from target coordinates on the map. To test the algorithm, we used two datasets of ligand binding affinity and showed that the proposed generator could produce diverse virtual compounds that had high activity in docking simulations.
authors.affiliation: Department of Chemical System Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan tel:(+81) 03-5841-7751.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Mishima
authors.affiliation: Department of Chemical System Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan tel:(+81) 03-5841-7751.
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Kaneko
authors.affiliation: Department of Chemical System Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan tel:(+81) 03-5841-7751. funatsu@chemsys.t.u-tokyo.ac.jp.
authors.forename: Kimito
authors.initials: K
authors.lastname: Funatsu
keywords: Chemical space; De novo design; Drug disco/very; Molecular diversity; Visualization of chemical space