Review
Computer Science, Interdisciplinary Applications
Joaquim R. R. A. Martins, Graeme J. Kennedy
Summary: This paper is a tribute to Raphael T. Haftka's significant contributions in multidisciplinary design optimization, focusing on adjoint method, wing aerostructural design optimization, and architectures for multidisciplinary design optimization. The overarching theme is the efficient computation of derivatives, enabling optimization with respect to large numbers of design variables even with costly high-fidelity models.
STRUCTURAL AND MULTIDISCIPLINARY OPTIMIZATION
(2021)
Review
Biochemistry & Molecular Biology
Sailan Shui, Stephen Buckley, Leo Scheller, Bruno E. Correia
Summary: Small-molecule responsive protein switches are important tools for controlling cellular processes, and recent advances in computational protein design have led to the development of switches that can respond to a wider range of small-molecule inducers with more sophisticated mechanisms.
Article
Biochemistry & Molecular Biology
Zukang Feng, John D. Westbrook, Raul Sala, Oliver S. Smart, Gerard Bricogne, Masaaki Matsubara, Issaku Yamada, Shinichiro Tsuchiya, Kiyoko F. Aoki-Kinoshita, Jeffrey C. Hoch, Genji Kurisu, Sameer Velankar, Stephen K. Burley, Jasmine Y. Young
Summary: The worldwide Protein Data Bank has collaborated with Global Phasing Ltd. and the Noguchi Institute to enhance validation reports for small molecules, including 2D diagrams and 3D electron density maps, to improve confidence in ligand conformation and interactions with macromolecules.
Article
Computer Science, Theory & Methods
Konstantinos Iliakis, Helga Timko, Sotirios Xydis, Panagiotis Tsapatsaris, Dimitrios Soudris
Summary: International high-energy particle physics research centers require extensive studies and simulations to plan for particle accelerators' upgrades and future machine designs. This article presents a highly optimized distributed version of the Beam Longitudinal Dynamics (BLonD) simulator, which leverages GPUs and approximate computing techniques to achieve significant speedups.
IEEE TRANSACTIONS ON PARALLEL AND DISTRIBUTED SYSTEMS
(2022)
Article
Chemistry, Medicinal
Renato Ferreira de Freitas, Yanli Liu, Magdalena M. Szewczyk, Naimee Mehta, Fengling Li, David McLeod, Carlos Zepeda-Velazquez, David Dilworth, Ronan P. Hanley, Elisa Gibson, Peter J. Brown, Rima Al-Awar, Lindsey James, Cheryl H. Arrowsmith, Dalia Barsyte-Lovejoy, Jinrong Min, Masoud Vedadi, Matthieu Schapira, Abdellah Allali-Hassani
Summary: This study identified the first antagonist that blocks the interaction between NSD2 and H3K36me2, providing a potential new approach for targeting NSD2 and further understanding its cellular function.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Pharmacology & Pharmacy
Ke Wu, Eduard Karapetyan, John Schloss, Jaydutt Vadgama, Yong Wu
Summary: In this article, the recent advancements in small molecule drug design are outlined with a focus on structural perspective. Protein structure prediction methods are compared and the role of ligand binding pocket in structure-based drug design is explored. Various structural features such as functional groups, stereochemistry, and molecular weight are examined for optimizing drug candidates. Computational tools like molecular docking and virtual screening are discussed for predicting and refining drug candidate structures. Examples of drug candidates designed based on their molecular structure are presented and future directions in the field are discussed. Integrating structural information with other valuable data sources can improve the drug discovery process, leading to the identification of novel therapeutics with improved efficacy, specificity, and safety profiles.
DRUG DISCOVERY TODAY
(2023)
Article
Chemistry, Multidisciplinary
Jianting Zhang, Jingbo Shi, Hang Zhao, Jinbo Bai, Xiaolin Li, Kunyue Leng
Summary: This study reports a crystal growth blocking strategy for the preparation of hierarchical UiO-66 MOFs using a solvent-free method. The addition of FeCl3 limits the overgrowth of UiO-66 crystals, resulting in particles with a size of approximately 12 nm. After removing Fe, these small particles loosely aggregate and gain intercrystalline mesopores. The optimized sample Mes-UiO-66 exhibits a well-developed hierarchical structure, with a BET surface area of 1161.9 m2 g-1 and a mesopore volume of 1.21 cm3 g-1. The catalytic performance and stability of Mes-UiO-66 are demonstrated by the oxidation of DBT, achieving a DBT conversion of over 99% with only a slight decrease after five cycles. This finding provides a novel platform for efficiently fabricating hierarchical MOFs for large-molecule catalysis.
CRYSTAL GROWTH & DESIGN
(2023)
Article
Chemistry, Multidisciplinary
Daniele Colarossi, Eleonora Tagliolini, Paolo Principi, Roberto Fioretti
Summary: This study presents an adjustable large-scale solar simulator based on metal halide lamps, which meets international standards for irradiance distribution and temporal stability. The simulator achieved different classes of standards on various test planes and successfully characterized a PV panel with good approximation using simulated radiation, outdoor sunlight, and numerical methods.
APPLIED SCIENCES-BASEL
(2021)
Article
Chemistry, Medicinal
Sebastian Dekkers, Birgit Caspar, Joelle Goulding, Nicholas D. Kindon, Laura E. Kilpatrick, Leigh A. Stoddart, Stephen J. Briddon, Barrie Kellam, Stephen J. Hill, Michael J. Stocks
Summary: In this study, fluorescent probes based on previously reported small-molecule antagonists were designed and synthesized using classic medicinal chemistry approaches to investigate the pharmacology and cellular distribution of the CXCR4 receptor. Three distinct chemical classes of fluorescent probes were developed and shown to specifically bind to the CXCR4 receptor in a fluorescence-based NanoBRET binding assay (pKD ranging 6.6-7.1). These probes were also used in competition binding experiments and confocal microscopy to further explore the pharmacology and cellular distribution of CXCR4.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Physical
Huan Zhao, Dan Zhang, Yueyue Yuan, Xueke Wu, Shaoxiang Li, Zhenjiang Li, Jianping Lai, Lei Wang
Summary: This study demonstrates a new method for synthesizing carrier-supported ultra-small immiscible alloy catalyst using solvent-free microwave reduction. The resulting Ru-based alloys show excellent performance in the alkaline electrocatalytic hydrogen evolution reaction, providing potential for the synthesis of nano-alloy supported catalysts.
APPLIED CATALYSIS B-ENVIRONMENTAL
(2022)
Article
Chemistry, Multidisciplinary
Niklas Heinemann, Juan Alcalde, Johannes M. Miocic, Suzanne J. T. Hangx, Jens Kallmeyer, Christian Ostertag-Henning, Aliakbar Hassanpouryouzband, Eike M. Thaysen, Gion J. Strobel, Cornelia Schmidt-Hattenberger, Katriona Edlmann, Mark Wilkinson, Michelle Bentham, R. Stuart Haszeldine, Ramon Carbonell, Alexander Rudloff
Summary: This article identifies the scientific challenges of large-scale underground hydrogen storage in porous media, highlighting the safety and economic impacts triggered by poorly understood key processes. Despite the vast opportunities provided by UHSP, its maturity is considered low, requiring multidisciplinary research to achieve safe, efficient and much-needed large-scale commercial deployment.
ENERGY & ENVIRONMENTAL SCIENCE
(2021)
Article
Pharmacology & Pharmacy
Yuan -Yuan Hei, Si Wang, Xiao-Xiao Xi, Hai-Peng Wang, Yuanxu Guo, Minhang Xin, Congshan Jiang, Shemin Lu, San-Qi Zhang
Summary: In this study, a series of fluoroquinolone derivatives were synthesized and compound A36 was found to be a potent and specific inhibitor of miRNA-21. A36 significantly reduced the expression of miRNA-21 and increased the expression of its target genes in HeLa cells. A36 exhibited antiproliferative activity against multiple tumor cell lines without cytotoxicity in normal cells. Furthermore, A36 induced apoptosis, arrested cells at the G(0)/G(1) phase, and inhibited cell-colony formation in HeLa cells. This study demonstrated that A36 is a novel miRNA-21 inhibitor.
JOURNAL OF PHARMACEUTICAL ANALYSIS
(2022)
Article
Multidisciplinary Sciences
Junpeng Xu, Guan Alex Wang, Lu Gao, Lang Wu, Qian Lei, Hui Deng, Feng Li
Summary: The authors report that small-molecule DNA binders can be used to program reaction pathways of a dynamic DNA reaction, where DNA strand displacement can be tuned quantitatively according to the affinity, charge, and concentrations of a given DNA binder. This binder-induced nucleic acid strand displacement (BIND) enables innovative technologies to accelerate the discovery and characterization of bioactive small molecules. They also demonstrate the application of a tandem BIND system as a high-throughput screening assay for discovering DNA binders.
NATURE COMMUNICATIONS
(2023)
Article
Engineering, Environmental
Yihui Yan, Dan Chang, Jiankun Liu, Anhua Xu, Mingyi Zhang, Yongjun Xie
Summary: This article introduces a new temperature-controlled large-scale direct shear apparatus (TXTZJ-500) that reduces the size effect on shear mechanical properties of geotechnical materials. Through testing sandy soil and graded gravel materials, the apparatus has shown stable and reliable performance.
COLD REGIONS SCIENCE AND TECHNOLOGY
(2023)
Article
Chemistry, Medicinal
Francesco Fiorentino, Martina Menna, Dante Rotili, Sergio Valente, Antonello Mai
Summary: RNA methylation is a crucial mechanism for regulating gene expression and RNA maturation. METTL3, an RNA methyltransferase, plays a key role in this process by adding a methyl group to N6-adenosine of RNA. Dysregulation of METTL3 can lead to various diseases and viral infections. By studying the correlation between METTL3 and diseases, as well as analyzing the development and mode of action of known METTL3 inhibitors, we can gain a better understanding of the biological functions of this enzyme and potentially develop new therapeutics.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Wei Wang, Yuzhi Lu, Enhui Chen, Kang Shen, Jun Li
Summary: A series of imidazo [1,2-a] pyridines designed from gossypol modification based on Groebke-Blackburn-Bienayme reaction were discovered as potent Bcl-2 inhibitors, showing good anti-proliferative activities for 7 human cancer cell lines. Compound 4 demonstrated the ability to suppress antiapoptotic proteins Bcl-2 and Bcl-X-L, with a possible binding model illustrated by molecular modeling.
BIOORGANIC CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Jonathan Edward King, David Ryan Koes
Summary: This article introduces a new dataset, SidechainNet, which extends ProteinNet and includes angle and atomic coordinate information for protein structures. By incorporating sidechain information, SidechainNet can describe all heavy atoms, and users can extend it to include new protein structures.
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
(2021)
Article
Chemistry, Physical
Xufang Chen, Dan Li, Yang Li, Weiting Zhan, Chao Huang, Rongsheng Chen, Wei Wang, Hongwei Ni, Paul K. Chu
Summary: A short-brush NiFeOxHy film with an edge-abundant, subcrystalline, and Ni3+-rich structure was designed and prepared on a Ni foam with a trace amount of Pt introduced to enhance water electrolysis performance. The short-brush NiFeOxHy film exhibited better OER activity than conventional nanosheets, while the Pt-modified materials showed effective HER catalytical activity. The alkaline electrolyzer composed of these electrodes required only 1.54 V to achieve a current density of 10 mA cm(-2).
APPLIED SURFACE SCIENCE
(2022)
Article
Chemistry, Multidisciplinary
Matthew Ragoza, Tomohide Masuda, David Ryan Koes
Summary: This study presents a deep learning system for generating 3D molecular structures conditioned on a receptor binding site, using an atomic density grid representation to train a conditional variational autoencoder. The properties of the generated molecules are evaluated, showing significant changes under different conditions such as mutated receptors. Sampling and interpolation techniques are used to explore the latent space learned by the generative model, allowing for end-to-end prediction of stable bioactive molecules from protein structures with deep learning.
Article
Chemistry, Medicinal
Andrew T. McNutt, David Ryan Koes
Summary: In this study, a Siamese convolutional neural network (CNN) is proposed for the prediction of relative binding free energy (RBFE) between two bound ligands. The network shows improved performance in RBFE prediction compared to a standard CNN, and its predictive performance varies among different protein families. Additionally, the RBFE prediction performance can be enhanced through few-shot learning during model training.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Biochemistry & Molecular Biology
Shabnam Shaabani, Louis Gadina, Ewa Surmiak, Zefeng Wang, Bidong Zhang, Roberto Butera, Tryfon Zarganes-Tzitzikas, Ismael Rodriguez, Justyna Kocik-Krol, Katarzyna Magiera-Mularz, Lukasz Skalniak, Alexander Domling, Tad A. Holak
Summary: Novel biphenyl-based chimeric compounds containing pomalidomide were found to exhibit strong inhibitory activity against PD-1/PD-L1, with compound 3 showing the best performance. Compounds 4 and 5 were able to significantly restore suppressed immunity in an ex vivo PD-1/PD-L1 blockade cell line bioassay.
Article
Biochemistry & Molecular Biology
Filipe Menezes, Grzegorz Maria Popowicz
Summary: In this study, three semi-empirical methods were used to model the interactions between the corannulene pincer and fullerenes. The results showed that these methods provided better agreement with experimental data compared to higher-level methods, at a significantly lower computational cost. Additionally, dynamical simulations were used to gain a more comprehensive understanding of the behavior of the corannulene pincer with fullerenes.
Article
Biochemistry & Molecular Biology
Domna Iordanidou, Michael G. Kallitsakis, Marina A. Tzani, Dimitris I. Ioannou, Tryfon Zarganes-Tzitzikas, Constantinos G. Neochoritis, Alexander Domling, Michael A. Terzidis, Ioannis N. Lykakis
Summary: This study reported the synthesis of 3,4-dihydroquinoxalin-2-ones through the selective reduction reaction catalyzed by supported gold nanoparticles. The reaction proceeded through heterogeneous transfer hydrogenation and intramolecular C-N transamidation, resulting in good functional-group tolerance and high yields.
Article
Chemistry, Multidisciplinary
Wei Wang, Yuzhi Lu, Juncheng Ge, Niya Liu
Summary: This study presents a practical and scalable route for the synthesis of 1,1'-dideoxygossypol from natural polyphenol product gossypol. The key steps involve regioselective deacetylation and reductive removal of hydroxyl groups. The study demonstrates that hydroxyl groups are not necessary for antitumor activities and that 1,1'-dideoxygossypol has improved aqueous solubility compared to gossypol.
Article
Environmental Sciences
Shamma AlMuraikhy, Najeha Anwardeen, Aisha Naeem, Maha Sellami, Alexander Domling, Abdelali Agouni, Mohamed A. Elrayess
Summary: This study aimed to analyze the metabolic profiles of young non-obese individuals and compare the effects of physical activity on insulin-sensitive and insulin-resistant groups. The results showed that physical activity had a positive impact on the health status of insulin-resistant individuals.
INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH
(2022)
Article
Chemistry, Analytical
Saeed Alshahrani, Abdullah Mohammed Al-Majid, M. Ali, Abdullah Saleh Alamary, Marwa M. M. Abu-Serie, Alexander Doemling, Muhammad Shafiq, Zaheer Ul-Haq, Assem Barakat
Summary: A new spiroxindoles with a benzimidazole scaffold was designed and synthesized as a new murine double minute two (MDM2) inhibitor. The desired spiroxindoles were obtained through a [3+2] cycloaddition reaction with excellent regioselectivity and diastereoselectivity. Biochemical assays showed that compound 7d exhibited the most active anticancer reactivity with an IC50 value of 3.797 +/- 0.205 μM. Compound 7a showed promising results as an MDM2 inhibitor with a KD value of 2.38 μM, as confirmed by molecular docking studies.
Article
Biochemistry & Molecular Biology
Shamma Almuraikhy, Najeha Anwardeen, Asmma Doudin, Maha Sellami, Alexander Domling, Abdelali Agouni, Asmaa A. Althani, Mohamed A. Elrayess
Summary: This study investigated the metabolic pathways involved in the protective effects of moderate physical activity in non-obese and healthy individuals. The results showed increased activation of antioxidative stress pathways in active participants, as well as significant associations between glutathione metabolites and certain clinical traits.
Article
Biochemistry & Molecular Biology
Shamma Almuraikhy, Najeha Anwardeen, Asmma Doudin, Maha Sellami, Alexander Domling, Abdelali Agouni, Asmaa A. Al Thani, Mohamed A. Elrayess
Summary: Healthy non-obese insulin resistant individuals have a higher risk of metabolic syndrome. Physical activity can lower insulin resistance, but the metabolic pathways involved are still unknown. This study analyzed data from 305 non-obese participants and found that active insulin resistant individuals showed differences in fatty acid metabolism, while sedentary insulin resistant individuals showed changes in glucose metabolism. These findings have important implications for the prevention and treatment of metabolic syndrome. Rating: 8 out of 10.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Computer Science, Interdisciplinary Applications
Zhonghua Xia, Pavel Karpov, Grzegorz Popowicz, Michael Sattler, Igor Tetko
Summary: Small-molecule drug design aims to identify inhibitors that can specifically bind to an enzyme's active site. Traditional methods rely on static structures to identify binding pockets, but small molecules can induce the opening of dynamic pockets. This study assessed the features in molecules that can induce cryptic pocket opening and developed a model to design inducers for undruggable proteins.
Article
Chemistry, Multidisciplinary
Harrison Green, David R. Koes, Jacob D. Durrant
Summary: Machine learning has been increasingly applied in the field of computer-aided drug discovery, showing notable advances in binding-affinity prediction, virtual screening, and QSAR. A deep convolutional neural network was used to predict appropriate fragments based on the structure of a receptor/ligand complex, with an efficiency of about 58% in selecting correct fragments from known ligands. The trained DeepFrag model and its associated software have been released under the Apache License, Version 2.0.