(4th-February-2020)
Various functions of cells are controlled by the interaction of molecules such as proteins. The basic principle in developing molecular targeted drugs using this mechanism is to search for compounds that bind to target proteins of cancer cells and pathogens and inhibit their functions (Figure 1). However, the structure of proteins in the living body (in solution) is soft and constantly changing. It is difficult to analyze such structural changes using ordinary structural analysis methods such as X-ray crystallography. Therefore, in recent years, "in silico drug discovery" has been attracting attention, in which a molecular simulation using a supercomputer (supercomputer) is used to reproduce the structural change of a target protein and to screen candidate compounds that bind to the target protein from a vast virtual compound library. You.
Figure 1 How targeted drugs act on proteins
A compound (ligand) serving as a drug exerts an effect such as inhibiting its function by strongly binding to a specific protein in the body.
In the simulation of protein structural changes, the forces acting between thousands or more atoms constituting a protein and the forces acting between these atoms and tens of thousands of water molecules surrounding a protein are calculated in steps of time. You. By repeatedly calculating the movement of all atoms from the calculation results, the movement of the entire protein is simulated as if the movie frame were advanced one frame at a time. This is a method called molecular dynamics (MD) calculation (Fig. 2), and it is characterized by a huge amount of time.
In the calculation of biomolecules, a motion of about 2 femtoseconds (2 × 10-15 seconds) is calculated as one frame. Large-scale structural changes in proteins in vivo are thought to occur on a time scale of microseconds (one millionth of a second) to milliseconds (one thousandth of a second) or more. To reproduce the movement of 100,000 atomic systems in 100 microseconds (1 × 10-4 seconds) in 2.5 femtoseconds (2.5 × 10-15 seconds), 40 billion (4 × 1010) frame calculations are required . With the current general-purpose supercomputer, it takes at least about 1 millisecond (1 × 10-3 seconds) to calculate each frame, so the time required for calculating 40 billion frames is at least 40 million seconds (4 × 107 seconds, About 1 year and 3 months).
Even if the performance of the supercomputer improves, it is difficult to reduce the time per frame to milliseconds or less in terms of design for general-purpose calculations. Therefore, the development of a special supercomputer that performs high-speed molecular simulation has been awaited.
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