出版者・発行元：American Chemical Society (ACS)  

The frozen domain (FD) approximation with fragment molecular orbital (FMO) method is efficient for partial geometry optimization of large systems. We implemented the FD formulation (FD and frozen domain dimer [FDD] methods) already proposed by Fedorov, D. G. et al. (J. Phys. Chem. Lett. 2011, 2 (4), 282–288.); proposed a variation of it, namely frozen domain and partial dimer (FDPD) method; and applied it to several protein-ligand complexes. The computational time for geometry optimization at the FDPD/HF/6-31G* level for the active site (six fragments) of the largest β2-adrenergic G protein-coupled receptor (440 residues) was almost half that of the conventional partial geometry optimization method. In the human estrogen receptor, the crystal structure was refined by FDPD geometry optimization of estradiol, surrounding hydrogen-bonded residues and a water molecule. The rather polarized ligand binding site of influenza virus neuraminidase was also optimized by FDPD optimization, which relaxed steric repulsion around the ligand in the crystal structure and optimized hydrogen bonding. For Serine-Threonine Kinase Pim1 and six inhibitors, the structures of the ligand binding site, Lys67, Glu121, Arg122, and benzofuranone ring and indole/azaindole ring of the ligand, were optimized at FDPD/HF/6-31G* and the ligand binding energy was estimated at the FMO-MP2/6-31G* level. As a result, the correlation coefficient between pIC50 and ligand binding energy was considerably improved as compared to results from both molecular mechanics- and quantum mechanics/molecular mechanics-optimized geometries. Thus, this approach is promising as a high-precision structure refinement method for structure-based drug discovery.

DOI： 10.26434/chemrxiv-2024-t9m7z

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掲載種別：研究論文（学術雑誌）  

DOI： 10.1002/celc.202481402

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担当区分：責任著者   掲載種別：研究論文（学術雑誌）   出版者・発行元：ChemElectroChem  

Although anion-exchange membranes (AEMs) are commonly used in fuel cells and water electrolyzers, their widespread commercialization is hindered by problems such as low anion conductivity and durability. Moreover, the development of high-performance AEMs remains complex and time consuming. Here, we address these challenges by proposing an innovative approach for the efficient design and screening of AEM polymers using unsupervised machine learning. Our model, which combines principal component analysis with uniform manifold approximation and projection, generates an intuitive map that clusters AEM polymers based on structural similarities without any predefined knowledge regarding anion conductivity or other experimentally derived variables. As a powerful navigation tool, this map provides insights into promising main-chain structures, such as poly(arylene alkylene)s with consistently high conductivity and polyolefins with exceptional performance depending on the substituent. Furthermore, assisted by key molecular descriptors, inverse analysis with this model allows targeted design and property prediction before synthesis, which will significantly accelerate the discovery of novel AEM polymers. This work represents a paradigm shift not only in AEM research but also generally in materials research, moving from black-box predictions toward interpretable guidelines that foster collaboration between researchers and machine learning for efficient and informed material development.

DOI： 10.1002/celc.202400252

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Journal of Physical Chemistry C  

Polymer wrapping techniques of single-walled carbon nanotubes (SWCNTs) are used for not only their solubilization in solvents but also tube structure separation and biosensor fabrication. Locally functionalized SWCNTs (lf-SWCNTs) contain defect sites that show bright defect photoluminescence (E11* PL) and exhibit sensitive and remarkable E11* PL energy shifts in response to changes in their surrounding dielectric environment. In this study, we exploited the E11* PL responsiveness of lf-SWCNTs to investigate polymer wrapping structures around nanotubes by analyzing four vinyl polymers. The observed E11* PL energy shifts clarify the unique microenvironment formation at the defect sites based on the polymer wrapping fashion differences: Namely, the side chains of the used polymers modulate the polymer wrapping tightness that change the amounts of D2O molecules accessing to the nanotube surfaces for local polarity variation near the defect sites, which induces the polymer-dependent PL shifts. Moreover, the substituents of the modified aryl groups in lf-SWCNTs contribute to the defect site polarity and hydrophobicity, by which a clear correlation between the substituent structures and the induced PL shifts is found. Therefore, the lf-SWCNT defect sites can produce unique molecular interaction fields showing E11* PL wavelength shift responses, which would contribute to development of advanced lf-SWCNT sensors.

DOI： 10.1021/acs.jpcc.3c07692

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Journal of Alzheimer's Disease  

Background: An association between poor oral health and cognitive decline has been reported. Most of these studies have considered the number of teeth as a criterion, only a few studies have analyzed the relationship between occlusal status and Alzheimer’s disease (AD). Objective: To elucidate whether posterior occlusal contact is associated with AD, focusing on the Eichner classification, among an older population aged 65 years or older in Japan. Methods: This study used monthly claims data of National Health Insurance in Japan from April 2017 to March 2020. The outcome was newly diagnosed AD defined according to ICD-10 code G30. The number of teeth was estimated by dental code data, and occlusal contact was divided into three categories, namely A, B, and C, according to the Eichner classification. Multivariate Cox proportional hazards models were used to analyze the association between a new diagnosis of AD and the Eichner classification. Results: A total of 22,687 participants were included, 560 of whom had newly diagnosed AD during a mean follow-up period of 12.2 months. The AD participants had a lower proportion of Eichner A and a higher proportion of Eichner C. After adjusting for covariates, hazard ratios (95% confidence intervals) with Eichner B and C were 1.34 (1.01–1.77) and 1.54 (1.03–2.30), respectively. Conclusion: In older people aged≥65 years old, reduced posterior occlusal contact as well as tooth loss have an impact on AD. This study emphasizes the importance of paying attention to occlusal contacts to reduce the risk of AD.

DOI： 10.3233/jad-230449

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Journal of Chemical Theory and Computation  

In all-atom (AA) molecular dynamics (MD) simulations, the rugged energy profile of the force field makes it challenging to reproduce spontaneous structural changes in biomolecules within a reasonable calculation time. Existing coarse-grained (CG) models, in which the energy profile is set to a global minimum around the initial structure, are unsuitable to explore the structural dynamics between metastable states far away from the initial structure without any bias. In this study, we developed a new hybrid potential composed of an artificial intelligence (AI) potential and minimal CG potential related to the statistical bond length and excluded volume interactions to accelerate the transition dynamics while maintaining the protein character. The AI potential is trained by energy matching using a diverse structural ensemble sampled via multicanonical (Mc) MD simulation and the corresponding AA force field energy, profile of which is smoothed by energy minimization. By applying the new methodology to chignolin and TrpCage, we showed that the AI potential can predict the AA energy with significantly high accuracy, as indicated by a correlation coefficient (R-value) between the true and predicted energies exceeding 0.89. In addition, we successfully demonstrated that CGMD simulation based on the smoothed hybrid potential can significantly enhance the transition dynamics between various metastable states while preserving protein properties compared to those obtained with conventional CGMD and AAMD.

DOI： 10.1021/acs.jctc.3c00889

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記述言語：日本語   出版者・発行元：公益社団法人 日本薬学会  

筆者は理論物理の出身で、さらには企業経験者である。その様な筆者が、なぜ創薬に関する研究をアカデミアで実施しているのか、その経緯を簡単ではあるが紹介させて頂く。振り返る中で、あらためて多くの人との出会いや支えがあっての今の自分であることを再認識することができた。この場を借りて御礼申し上げるとともに、期待に応えられるように今後も邁進していく所存である。

DOI： 10.14894/faruawpsj.60.1_59_1

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記述言語：日本語   出版者・発行元：一般社団法人 人工知能学会  

<p>現代社会を支える基幹材料である機能性高分子は、実験を中心に盛んに研究されているが、人工知能（AI）や機械学習（ML）の導入による更なる効率化が期待されている。しかしながら、透明性・解釈性の低いMLモデルでは実験研究者からの信頼を得にくい。本研究では、機能性高分子材料の1つであるアニオン伝導膜の物性予測のための説明可能AI(XAI)を構築し、その透明性・解釈性を評価した。当研究の流れは①独自データベース(DB)の構築、②既存記述子を用いた高分子構造の数値化、③MLモデルの構築、④各説明変数のShapley(SHAP)値を算出し解析した。①本研究で対象としたアニオン伝導膜の構造・物性については公開DBが存在しないため、300弱の構造・物性データを論文から収集してDB化した。次に、②と③を実施した結果、テストデータに対してR2=0.7983の予測精度を持つモデルを得た。④では高分子構造記述子由来のAMID_Nが重要であることが示された。AMID_Nは高分子構造内の物性と密に相関する記述子であり、化学的な解釈・理解を後押しし、実験へのフィードバックが可能なXAIの構築に成功した。</p>

DOI： 10.11517/pjsai.jsai2024.0_1f4gs1002

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記述言語：日本語   出版者・発行元：The Japanese Society for Artificial Intelligence  

<p>The evaluation of protein-drug molecule interactions through molecular simulation plays a critical role in identifying drug candidates from a vast pool of chemical compounds in computational drug discovery. To increase the hit rate, which has been a challenge with traditional methods, accurate quantum chemical calculations of protein-drug molecule interactions are necessary. However, evaluating protein-drug molecule interactions using conventional quantum chemistry calculation methods is challenging. The Fragment Molecular Orbital (FMO) method allows for the calculation of protein-drug molecule interactions with quantum chemistry accuracy. Still, even using the "Fugaku" supercomputer, it takes several hours per structure, indicating a need for further reduction in computational costs. This study presents a machine learning model that predicts interaction values between proteins and drug molecules using the FMO method. This model is based on a neural network and utilizes vectors of the surrounding environment of each atom in the drug molecule as explanatory variables. Using a dataset of approximately 2000 structures, the model was trained and tested for predicting interactions in unknown structures. The model successfully predicted protein-drug molecule interactions with an R2 value of 0.59.</p>

DOI： 10.11517/pjsai.jsai2024.0_4q3is2d05

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Scientific Reports  

Abstract

Neutral radicals, including carbon radicals, are highly useful chemical species for the functionalization of semiconducting materials to change their electrical and optical properties owing to their high reactivity. However, boron radicals have been limited to synthetic and reaction chemistry, with rare utilization in materials science. In this study, a mixture of tetrahydroxydiboron (B₂(OH)₄) and pyridine derivatives was found to act as an electron dopant for single-walled carbon nanotubes (SWCNTs) because of the electron transfer from pyridine-mediated boron radicals generated by B–B bond dissociation to neutral radicals. In particular, the radical formed from a mixture of B₂(OH)₄ and 4-phenylpyridine ((4-Phpy)B(OH)₂^·) efficiently doped electrons into the SWCNT films; thus, n-type SWCNTs with long-term air stability for more than 50 days at room temperature were prepared. Furthermore, the experimental and theoretical surface analyses revealed that the formation of stable cations from ((4-Phpy)B(OH)₂^·) and the efficient interaction with SWCNTs due to their high planarity served as the mechanism for their stable doping.

DOI： 10.1038/s41598-023-48847-2

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その他リンク： https://www.nature.com/articles/s41598-023-48847-2

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： https://doi.org/10.1273/cbij.23.14

担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：情報計算化学生物学会(CBI学会)  

The fragment molecular orbital (FMO) method enables quantum mechanical calculations for macromolecules by dividing the target into fragments. However, most calculations, even for metalloproteins, have been performed by removing metal ions from the structures registered in the Protein Data Bank (PDB). For more realistic and useful calculations, FMO calculations must be performed without removing the metal ions. In this study, we discuss the results obtained from FMO calculations performed using 6-31G* and model core potentials (MCPs) for metal proteins containing Zn and Mg ions. Subsequently, we analyze the differences in atomic charges and interactions.

DOI： 10.1273/cbij.23.14

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：日本結晶学会  

DOI： 10.5940/jcrsj.65.17

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記述言語：その他   掲載種別：研究論文（学術雑誌）   出版者・発行元：International Journal of Environmental Research and Public Health  

This study aimed to investigate the association between dietary problems and frailty according to tooth loss in older Japanese people. This cross-sectional study included 160 older people (mean age 82.6 years) from Japan. Frailty status was assessed using the Study of Osteoporotic Fractures (SOF) criteria, which consists of (i) weight loss > 5% in the past year, (ii) inability to perform five chair stands, and (iii) self-perceived reduced energy level. Frailty was defined as the presence of ≥2 items of SOF criteria. Multivariate logistic regression analyses were performed with frailty as the dependent variable and dietary problems as the independent variable, stratified according to having <20 teeth. Low appetite and no enjoyment of eating were associated with frailty after adjusting for covariates in participants with <20 teeth. Dietary problems, including low appetite, eating alone, and negative attitudes toward enjoyment of eating were associated with a self-perceived reduced energy level in participants with <20 teeth. However, this association was not observed in participants with ≥20 teeth. In older people with fewer teeth, dietary problems have been suggested to be associated with frailty. Therefore, it may be necessary to pay attention to dietary problems, especially in older people with tooth loss.

DOI： 10.3390/ijerph192316260

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記述言語：その他   掲載種別：研究論文（学術雑誌）   出版者・発行元：ACS Nano  

Defect functionalization of single-walled carbon nanotubes (SWCNTs) by chemical modification is a promising strategy for near-infrared photoluminescence (NIR PL) generation at >1000 nm, which has advanced telecom and bio/medical applications. The covalent attachment of molecular reagents generates sp3-carbon defects in the sp2-carbon lattice of SWCNTs with bright red-shifted PL generation. Although the positional difference between proximal sp3-carbon defects, labeled as the defect binding configuration, can dominate NIR PL properties, the defect arrangement chemistry remains unexplored. Here, aryldiazonium reagents with π-conjugated ortho-substituents (phenyl and acetylene groups) were developed to introduce molecular interactions with nanotube sidewalls into the defect-formation chemical reaction. The functionalized chiral SWCNTs selectively emitted single defect PL in the wavelength range of ∼1230-1270 nm for (6,5) tubes, indicating the formation of an atypical binding configuration, different from those exhibited by typical aryl- or alkyl-functionalized chiral tubes emitting ∼1150 nm PL. Moreover, the acetylene-based substituent design enabled PL brightening and a subsequent molecular modification of the doped sites using click chemistry.

DOI： 10.1021/acsnano.2c09897

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記述言語：その他   掲載種別：研究論文（学術雑誌）  

DOI： 10.1021/acs.jcim.1c00694

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DOI： 10.1007/978-981-15-9235-5_21

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DOI： 10.1007/978-981-15-9235-5_4

記述言語：その他   掲載種別：研究論文（学術雑誌）  

DOI： 10.1002/jcc.26190

記述言語：その他   掲載種別：研究論文（学術雑誌）  

DOI： 10.2477/jccj.2019-0030

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1074/jbc.RA119.011463

記述言語：その他   掲載種別：研究論文（学術雑誌）  

DOI： 10.7567/1347-4065/ab5335

記述言語：その他   掲載種別：研究論文（学術雑誌）  

DOI： 10.2477/jccj.2019-0016

記述言語：その他   掲載種別：研究論文（学術雑誌）  

DOI： 10.1063/1.5000091

記述言語：その他   掲載種別：研究論文（学術雑誌）  

DOI： 10.2477/jccj.2017-0051

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.cplett.2015.03.057

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1103/PhysRevB.85.115448

記述言語：その他   掲載種別：研究論文（学術雑誌）  

DOI： 10.1088/1742-6596/302/1/012007

記述言語：英語   掲載種別：研究論文（その他学術会議資料等）  

DOI： 10.1016/j.physe.2010.07.025

記述言語：その他   掲載種別：研究論文（学術雑誌）  

DOI： 10.1557/proc-1204-k18-02

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1002/anie.200902468

開催年月日： 2023年7月

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開催年月日： 2022年3月

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開催年月日： 2021年12月

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記述言語：日本語   出版者・発行元：(一社)日本疫学会  

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記述言語：日本語   出版者・発行元：(一社)日本疫学会  

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記述言語：日本語   出版者・発行元：(一社)日本疫学会  

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J-GLOBAL

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J-GLOBAL

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種別：審査・学術的助言 

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対象： 社会人・一般,　学術団体,　企業,　市民団体,　行政機関

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対象： 社会人・一般,　学術団体,　企業,　市民団体,　行政機関

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対象： 社会人・一般,　学術団体,　企業,　市民団体,　行政機関

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対象： 社会人・一般,　学術団体,　企業,　市民団体,　行政機関

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