Fujitsu and PeptiDream have agreed to initiate joint research and development in the area of peptide drug discovery, using Fujitsu’s Digital Annealer, which employs next-generation computing architecture to quickly solve combinatorial optimisation problems.

By combining Fujitsu’s proprietary high-speed, quantum-inspired computing technology with PeptiDream’s advanced knowledge and wealth of experimental data in unique peptides, the companies seek to develop revolutionary in silico drug discovery technology.

This technology, applied to the field of peptide drug discovery offers researchers the chance to dramatically accelerate the search for drug candidate compounds through improved efficiency.

At present, the most widely distributed drugs are small-molecule drugs, which have the advantages, as oral drugs, of being relatively cost-effective and easy to develop. On the other hand, because their selectivity toward the target is low, they have the disadvantage of acting on off-target areas, making them prone to causing side-effects.

In contrast, antibody drugs, which are large-molecule drugs, are costly, but because they are highly selective cause relatively few side-effects. Peptide therapeutics, which have a molecular weight in between small-molecule drugs and antibody drugs, combine the advantages of low-cost with relatively few side effects.

The drug discovery process for peptides involves extracting thousands of candidates from a starting point of several trillions of candidate compounds, and then further whittling that number down to several tens of candidates. This search process requires an iterative process in which, in addition to “dry” experiments that can be simulated with computers, there are “wet” experiments performed in the lab.

Ordinarily, this process takes anywhere from a few months to a few years. In the process of narrowing down candidate compounds, it remains important to have an understanding of a molecule’s stable conformation. In an analysis using a conventional computer, however, getting information on the stable conformation of one compound would take several days.

For combinatorial optimisation problems, which take into account various combinations of real-world factors to discover an optimal solution, Fujitsu began offering the services of the Digital Annealer in May 2018. Fujitsu Laboratories originally developed the hardware using next-generation architecture inspired by quantum phenomena.

The Digital Annealer’s ability to rapidly locate optimal solutions for problems that could not be solved using conventional computers, makes it an ideal choice for applications in a wide range of areas, including delivery optimisations in distribution, the optimisation of component placement in a factory, portfolio optimisation in finance, and narrowing candidate selection in materials and drug discovery.

For drug discovery, PeptiDream has a proprietary drug discovery and development platform called the Peptide Discovery Platform System, which enables it to freely create unique peptides that have a variety of unnatural amino acids and accelerate searches for drug candidate compounds.

PeptiDream is leveraging this system to move forward with the development of a large number of drug candidate compounds targeting a wide range of indications that could not be targeted with conventional small-molecule drugs or antibodies.

By introducing the Digital Annealer to these efforts, Fujitsu and PeptiDream aim to accelerate the search process for candidate compounds in PeptiDream’s peptide drug discovery process, jointly developing and validating their peptide drug discovery technology.

In peptide drug discovery, it is important to obtain information on the peptide’s stable conformation, which is determined by the structure of its main and side chains.

In this collaboration between Fujitsu and PeptiDream, combinatorial optimisation calculations will be performed using Fujitsu’s Digital Annealer to verify whether stable conformations of unique peptides can be quickly obtained. Researchers will rely on PeptiDream’s huge database of unique peptides.

The joint research seeks to create search technology for the stable conformations of unique peptides and verify the usefulness of the Digital Annealer in peptide drug discovery.

By applying the Digital Annealer technology to the search process in PeptiDream’s candidate compound development, the two companies aim to significantly reduce search times from a few days to a fraction of that time, dramatically improving the efficiency of discovering drug candidate compounds, and helping to improve the prospects of bringing about new drugs.

Naoko Yoshizawa, executive vice-president of Fujitsu, comments: “Fujitsu is leveraging its Digital Annealer to achieve solutions to a wide range of challenging issues confronting society. The technology’s unique architecture allows it to quickly solve combinatorial optimization problems that have proven very difficult to solve using conventional computers because of the huge volume of calculations required.

“With this initiative, Fujitsu will play an instrumental role in developing a revolutionary technology for searching for compounds that offers high speed and high precision, addressing the challenge presented by the amount of time required for the lengthy peptide drug discovery process and making the time spent on searches dramatically more efficient.

“We hope to contribute to the creation of innovative new drugs through the synergistic effect of our collaboration with PeptiDream, which leads the field of mid-molecule drug discovery with its advanced knowledge and innovative technology, and our efforts utilizing our own cutting-edge computing technology.”

Dr Keiichi Masuya, executive vice-president of PeptiDream, adds: “In searching and optimizing unique peptides, it is very important to have an understanding of a peptide’s stable conformation in water and its stable conformation when the peptide interacts with a protein. In analyses using conventional computers, even at their fastest, these calculations took several days.

“We are very pleased to collaborate with Fujitsu and its Digital Annealer on the potential for reducing the time required for these calculations to a fraction of what is required today.

“Through this collaboration, we would like to substantially improve the efficiency of the unique peptide search process and contribute even further to the creation of innovative new drugs.”