Business Summary

The Technology Research Association for Next-Generation Natural Products Chemistry (N2PC) has been developing cutting-edge technologies for developing medium-sized molecular simulation technology aiming at control of PPI within the cell. In this project, using cryo-electron microscopy and nuclear magnetic resonance (NMR), N2PC can analyze structural polymorphisms, and simulate medium-sized-molecule membrane permeability using in silico technology and their experimental data.

In addition, to achieve the above research aims efficiently, N2PC will also carry out the development of a high-resolution cryo-electron microscope that is optimal for single-particle analysis.

Contents

To accelerate drug discovery for medium-sized molecules, it is necessary to develop basic technology that enables prediction of the membrane permeability and the binding to a target molecule. Because the diversity in chemical structures of the target medium-sized molecular compounds becomes large compared to those in small-molecule drug discovery, the structure of the drug enables penetration of the biological membrane and becomes a drug discovery target before actual synthesis. We are developing evaluation / prediction simulation technology to narrow down in advance whether specific effects can be realized. As research and development items we are currently undertaking the following:

• Development of simulation technology based on demonstrated prediction of structural features with membrane permeability
• Support of results utilization / drug discoDemonstration of protein-protein interaction PPI and other intracellular drug discovery tools to facilitate searches for medium-sized molecules, and development of structure optimization technology. In addition, the basic design for the development of a high-resolution cryo-electron microscope suitable for single-particle analysis has been completed, and production is aimed for completion in 2019.