Home | Research Center for Computational Science

Molecular Simulation × AI Reveals Structural Changes of Transporter Proteins

Transporter proteins exist in the plasma membrane and transport various substrates into and out of the cell. It is believed that substrates are transported by a mechanism involving conformational changes called alternating access. Therefore, it is necessary to elucidate the structural changes in order to understand the mechanism. We have elucidated the conformational changes of the oxalate transporter, which transports oxalic acid, a substance contained in vegetables and nuts that causes urinary tract stones, by combining molecular dynamics (MD) simulations and the structure prediction AI AlphaFold. MD simulations predicted the inward-open conformation, which is experimentally difficult to analyze, and AlphaFold successfully predicted mutations that stabilize the inward-open conformation.

Accelerated Molecular Dynamics and AlphaFold Uncover a Missing Conformational State of Transporter Protein OxlT
J. Ohnuki, T. Jaunet-Lahary, A. Yamashita, and K. Okazaki, J. Phys. Chem. Lett. 15, 725–732 (2024).

Electronic structure informatics to search for hightly efficient photovoltaic materials using singlet fission

The transition from fossil fuels to environment-friendly and renewable sources of energy has become one of the central challenges for today’s society and across scientific disciplines. Though global energy studies report that there has been record-breaking growth in sustainable energy production, further improvements are desirable. Solar energy is a promising solution for the near future, owing to its availability and potentially high output.

In this study, an "electronic structure informatics" approach combining the semiempirical molecular orbital method, time-dependent density functional theory, and machine learning has been applied to rapidly search for materials that can be used as photovoltaic cell materials with high efficiency by multiple exciton generation using singlet fission from over 4 million derivatives based on indigo, a famous dye of natural origin. The obtained promising candidate molecules and their possible candidates were identified and compared with those not. Random forest classification of the chemical structures of the obtained promising and non-promising candidate molecules led to the discovery of chemical structure rules that effectively show singlet fission and the identification of candidate materials with symmetric chemical structures and sufficient synthesizability in the order of several hundred.

Weber F., Mori H., npj Comput. Mater., 8, 176 (2022).

Electronic structure informatics to search for hightly efficient photovoltaic materials using singlet fission

The transition from fossil fuels to environment-friendly and renewable sources of energy has become one of the central challenges for today’s society and across scientific disciplines. Though global energy studies report that there has been record-breaking growth in sustainable energy production, further improvements are desirable. Solar energy is a promising solution for the near future, owing to its availability and potentially high output.

In this study, an "electronic structure informatics" approach combining the semiempirical molecular orbital method, time-dependent density functional theory, and machine learning has been applied to rapidly search for materials that can be used as photovoltaic cell materials with high efficiency by multiple exciton generation using singlet fission from over 4 million derivatives based on indigo, a famous dye of natural origin. The obtained promising candidate molecules and their possible candidates were identified and compared with those not. Random forest classification of the chemical structures of the obtained promising and non-promising candidate molecules led to the discovery of chemical structure rules that effectively show singlet fission and the identification of candidate materials with symmetric chemical structures and sufficient synthesizability in the order of several hundred.

Weber F., Mori H., npj Comput. Mater., 8, 176 (2022).

The mechanism of divalent cation block of ion channel activity

Nervous activity is subjected to complex regulation by ion channels. In this study, we reproduced the divalent cations block in molecular dynamics simulation and elucidated the blocking mechanism. It was observed that introducing a hydrophilic environment into the channel lumen allows the stable existence of divalent cations. This retention of divalent cations makes it difficult for ions to permeate the ion channel. This result also provides new knowledge about the reproduction of polyvalent ions in molecular dynamics simulations.

K. Irie, Y. Oda, T. Sumikama, A. Oshima, Y. Fujiyoshi, Nat. Commun., 14, 4236 (2023).

The mechanism of divalent cation block of ion channel activity

Nervous activity is subjected to complex regulation by ion channels. In this study, we reproduced the divalent cations block in molecular dynamics simulation and elucidated the blocking mechanism. It was observed that introducing a hydrophilic environment into the channel lumen allows the stable existence of divalent cations. This retention of divalent cations makes it difficult for ions to permeate the ion channel. This result also provides new knowledge about the reproduction of polyvalent ions in molecular dynamics simulations.

K. Irie, Y. Oda, T. Sumikama, A. Oshima, Y. Fujiyoshi, Nat. Commun., 14, 4236 (2023).

Au-Ag nanoclusters showing intense phosphorescence in cells

Luminescent metal nanoclusters are expected to exhibit unique physical properties in the cluster structure depending on the ligand structure, metal type, number of nuclei and arrangement. In this study, carbon-centered gold-silver (CAu₆Ag₂) clusters with N-heterocyclic carbene (NHC) ligands were designed and synthesized, and it was found that these clusters emit strong phosphorescence in solution, and the contribution of NHC ligands to phosphorescence emission was revealed by theoretical calculation. The luminescence rate constant was calculated by an analysis including spin-orbit interactions, and the quantum yield was discussed in terms of the energy barrier to the minimum energy crossing point. Furthermore, the phosphorescent gold-silver clusters with long luminescence lifetime were used for cellular imaging, which revealed the pathway of uptake into the cell and selective localization to specific organelles, confirming their superior functionality, which is different from the non-selective uptake of conventional phosphine ligands.
Z. Lei, M. Endo, H. Ube, T. Shiraogawa, P. Zhao, K. Nagata, X.-L. Pei, T. Eguchi, T. Kamachi, M. Ehara, T. Ozawa, M. Shionoya Nature Commun. 13, 4288-1-9 (2022).

Au-Ag nanoclusters showing intense phosphorescence in cells

Luminescent metal nanoclusters are expected to exhibit unique physical properties in the cluster structure depending on the ligand structure, metal type, number of nuclei and arrangement. In this study, carbon-centered gold-silver (CAu₆Ag₂) clusters with N-heterocyclic carbene (NHC) ligands were designed and synthesized, and it was found that these clusters emit strong phosphorescence in solution, and the contribution of NHC ligands to phosphorescence emission was revealed by theoretical calculation. The luminescence rate constant was calculated by an analysis including spin-orbit interactions, and the quantum yield was discussed in terms of the energy barrier to the minimum energy crossing point. Furthermore, the phosphorescent gold-silver clusters with long luminescence lifetime were used for cellular imaging, which revealed the pathway of uptake into the cell and selective localization to specific organelles, confirming their superior functionality, which is different from the non-selective uptake of conventional phosphine ligands.
Z. Lei, M. Endo, H. Ube, T. Shiraogawa, P. Zhao, K. Nagata, X.-L. Pei, T. Eguchi, T. Kamachi, M. Ehara, T. Ozawa, M. Shionoya Nature Commun. 13, 4288-1-9 (2022).

“Bucket brigade” of remdesivir in RNA-dependent RNA polymerase of SARS-CoV-2

　The process of remdesivir uptake into the protein (RNA-dependent RNA polymerase) that replicates the gene of SARS-CoV-2 was revealed by molecular dynamics simulations. Remdesivir has a phosphate group with a negative charge, and the binding site of RNA polymerase has Mg²⁺ ions. In addition, RNA polymerase has lysine residues, which are positively charged, in a line toward the binding site. It was found that the lysine residue attracts the phosphate group of remdesivir and passes it to the next lysine residue sequentially, transporting the drug to the binding site like a bucket brigade.

S. Tanimoto, S. G. Itoh, and H. Okumura: Biophys. J. (2021), DOI: 10.1016/j.bpj.2021.07.026, “Bucket brigade” using lysine residues in RNA-dependent RNA polymerase of SARS-CoV-2

“Bucket brigade” of remdesivir in RNA-dependent RNA polymerase of SARS-CoV-2

　The process of remdesivir uptake into the protein (RNA-dependent RNA polymerase) that replicates the gene of SARS-CoV-2 was revealed by molecular dynamics simulations. Remdesivir has a phosphate group with a negative charge, and the binding site of RNA polymerase has Mg²⁺ ions. In addition, RNA polymerase has lysine residues, which are positively charged, in a line toward the binding site. It was found that the lysine residue attracts the phosphate group of remdesivir and passes it to the next lysine residue sequentially, transporting the drug to the binding site like a bucket brigade.

S. Tanimoto, S. G. Itoh, and H. Okumura: Biophys. J. (2021), DOI: 10.1016/j.bpj.2021.07.026, “Bucket brigade” using lysine residues in RNA-dependent RNA polymerase of SARS-CoV-2

Scientific results using RCCS

Update Information

2025-02-17	Start of Open OnDemand Service
We are pleased to announce the launch of Open OnDemand, a web browser-based portal service that makes our supercomputer more accessible. This service enables you to access the system directly through your web browser, execute GUI applications, and perform file operations. Read more about Start of Open OnDemand Service

2025-03-14	Molpro 2025.1.0 installed
Molpro 2025.1.0 has been installed. Read more about Molpro 2025.1.0 installed

2025-03-10	OpenBabel 3.1.1 installed
OpenBabel 3.1.1 has been installed under /apl/openbabel/3.1.1. Read more about OpenBabel 3.1.1 installed

2024-05-01	May 9 (Thu) 9:00-17:00 NOUS maintenance
Application submission system NOUS will be unavailable from 9:00 to 17:00 on Thursday, May 9 due to the scheduled maintenance. Thank you for your understanding. Read more about May 9 (Thu) 9:00-17:00 NOUS maintenance