The chemical space project.

Area of Science:

• Computational Chemistry
• Medicinal Chemistry
• Chemical Informatics

Background:

• Understanding the full scope of molecular diversity is crucial for scientific advancement.
• Previous efforts to enumerate chemical space were limited in scale and scope.

Purpose of the Study:

• To computationally enumerate all possible organic molecules up to a specific size to explore chemical space.
• To create the largest small molecule database to date (GDB-17) for unbiased insight into molecular diversity.
• To develop tools for virtual screening and visualization of large chemical databases.

Main Methods:

• Computational enumeration of organic molecules up to 17 atoms (C, N, O, S, halogens).
• Exclusion of unstable or nonsynthesizable molecules based on valency rules, topology, and functional groups.
• Development of visualization tools including a "periodic system of molecules" and principal component maps (MQN- and SMIfp-Mapplet).

Main Results:

• Creation of GDB-17, containing 166.4 billion unique organic molecules.
• Demonstration of the vastness of chemical space, with millions of close analogs readily identifiable for any given molecule.
• Successful proof-of-concept applications in drug discovery through virtual screening, synthesis, and activity testing.

Conclusions:

• The GDB-17 database provides an unprecedented resource for exploring chemical diversity.
• The depth of chemical space allows for rapid identification of numerous drug analogs.
• Future challenges include enumerating larger molecules and synthesizing novel GDB compounds.