Article
Chemistry, Multidisciplinary
Ling Wu, Wei Shao, Qun Cao, Zheng Cui
Summary: The study investigates the effects of the wettability and volume of depositional nanoparticles on nanoscale liquid film evaporation, finding that increasing wettability enhances heat transfer and increasing volume improves heat transfer performance. These findings provide insights into the impact of depositional nanoparticles on engineering applications.
Article
Biochemical Research Methods
Damien Jefferies, Syma Khalid
Summary: Membrane proteins are amphipathic macromolecules with diverse chemical compositions and biological functions. Traditional experimental techniques and molecular modeling software, especially molecular dynamics algorithms, can provide comprehensive insights into the properties and dynamic behaviors of membrane proteins.
Article
Materials Science, Ceramics
Xing Luo, Zhibo Zhang, Yongnan Xiong, Yao Shu, Jiazhen He, Kaihong Zheng, Yuan Bao, Herbert M. Urbassek
Summary: Molecular dynamics simulation is used to study phase transformations during nanoindentation into the (0001) surface of monocrystalline AlN with wurtzite structure. The results show that with increasing indentation depth, surface tearing, nucleation and growth of a graphite-like phase, formation and flow of an amorphous phase, and generation of a tetragonal intermediate structure occur consecutively. The findings are consistent across a wide range of indentation speeds from 10-160 m/s.
CERAMICS INTERNATIONAL
(2021)
Article
Materials Science, Multidisciplinary
Rongyang Qiu, Yangchun Chen, Xichuan Liao, Xinfu He, Wen Yang, Wangyu Hu, Huiqiu Deng
Summary: The development of V-Ti-Ta interatomic potential is a significant step towards the atomic-scale investigation of V-based alloys, which fits well with experimental data and DFT calculations and can be used for atomistic simulations of point defects evolution.
JOURNAL OF NUCLEAR MATERIALS
(2021)
Article
Chemistry, Multidisciplinary
Kang Xia, Haifei Zhan, Xinjie Zhang, Zhiyong Li
Summary: This study investigates the impact resistance and deformation mechanisms of 2D titanium carbide MXene materials. The results show a positive correlation between the number of titanium atom layers and the penetration energy. Ti2C nanosheets exhibit the most significant elastic wave propagation velocity and energy dissipation, leading to higher specific penetration energy. These findings provide insights for the development of impact protection applications.
Article
Materials Science, Multidisciplinary
Ayrat A. A. Nazarov, Dmitry V. V. Bachurin, Zenglei Ni
Summary: In this study, molecular dynamics simulations were conducted to investigate the interface sliding, dislocation emission, temperature changes, porosity variation, and structure evolution during ultrasonic welding of copper at the atomic level. The results contribute to a better understanding of the physical processes occurring during ultrasonic welding of metals.
Article
Engineering, Mechanical
Dongpeng Hua, Qiaosheng Xia, Yeran Shi, Qing Zhou, Shuo Li, Xiangtao Deng, Haifeng Wang, Zhaodong Wang
Summary: The deformation response of the cementite/ferrite (Fe3C/alpha-Fe) interface under a mechanical load was investigated using molecular dynamics simulation. The results revealed that the interface effectively hinders shear deformation propagation and relaxes strain/stress concentration. With increasing indentation depth, the cementite phase undergoes an amorphous transformation and rejuvenation, while the ferrite phase undergoes a phase transformation to HCP, synergistically enhancing the plasticity of pearlite. Furthermore, the study shed light on the underlying origin for the decreased growth rate of the friction coefficient with increasing friction depth and the periodic changes in tribological properties in the scratch direction.
TRIBOLOGY INTERNATIONAL
(2023)
Article
Biochemistry & Molecular Biology
Juntamanee Jewboonchu, Jirakrit Saetang, Dennapa Saeloh, Thanyaluck Siriyong, Thanyada Rungrotmongkol, Supayang Piyawan Voravuthikunchai, Varomyalin Tipmanee
Summary: The study revealed the mechanism of action of conessine against Pseudomonas aeruginosa's efflux pump, including its impact on glycine loop flexibility and binding site in the efflux pump. This could serve as a key for designing and developing novel EPIs against multidrug-resistant P. aeruginosa.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Chemistry, Physical
Xiaorong Liu, Dongpeng Hua, Wan Wang, Qing Zhou, Shuo Li, Junqin Shi, Yixuan He, Haifeng Wang
Summary: This study investigated the initial dislocation nucleation and motion mechanisms in TaTiZrV high-entropy alloys (RHEAs) and their dependence on temperature through molecular dynamics simulations. The short-range orders in the RHEA facilitate preferential inhomogeneous nucleation at low stress, while compositional fluctuation affects the slipping and moving rate of dislocations. Moreover, the difficulty of initial dislocation nucleation increases with temperature.
JOURNAL OF ALLOYS AND COMPOUNDS
(2022)
Article
Chemistry, Physical
Shanshan Shi, Qiudan Wang, Sai Liu, Zhiyuan Qu, Kaihang Li, Xiaoju Geng, Tao Wang, Jian Gao
Summary: By linking the structures of resveratrol molecules RSV1 and RSV2, four novel SIRT1 activators were constructed, two of which showed higher binding interaction with SIRT1 compared to RSV1, 2, and significantly promoted the binding of p53-AMC peptide to SIRT1. These findings suggest potential for the rational design of more promising SIRT1 activators in the future.
Article
Engineering, Mechanical
Dongpeng Hua, Qiaosheng Xia, Wan Wang, Qing Zhou, Shuo Li, Dan Qian, Junqin Shi, Haifeng Wang
Summary: Understanding contact-induced behavior in metals is crucial for studying mechanical properties. Nanoindentation studies on CoCrNi MEA revealed unique dislocation nucleation at Cr-rich clusters, contrary to conventional homogeneous nucleation in pure metals. Compositional inhomogeneity and temperature were found to influence defect behavior, with nanotwin formation and phase-transformation promoted at low temperatures.
INTERNATIONAL JOURNAL OF PLASTICITY
(2021)
Article
Chemistry, Physical
Hongru Ding, Pavana Siddhartha Kollipara, Linhan Lin, Yuebing Zheng
Summary: Optothermal tweezers, with superior manipulation capability at low optical intensity, are limited by implicit understanding of the working mechanism. By revealing the atomistic view of opto-thermo-electro-mechanic coupling, we have developed high-performance tweezers using low-concentrated electrolytes and demonstrated their efficiency in separating colloidal particles based on surface charge differences.
Article
Engineering, Mechanical
Jian Guo, Shilian Tan, Chen Xiao
Summary: In this study, the scratching-induced material removal behavior and mechanism of single-crystal AlN using single diamond abrasive were investigated through molecular dynamics simulation and nanowear test. The results showed that the plasticity-dominated nanowear of AlN can be properly described with the Archard-type model, linearly relating wear volume to normal load within a limited load range but not at high loads.
TRIBOLOGY INTERNATIONAL
(2022)
Article
Polymer Science
Wesley Michaels, Yan Zhao, Jian Qin
Summary: The study developed all-atom force fields for undoped and highly doped PEDOT systems, which showed significant improvements in simulating molecular structures and properties compared to GAFF. Meaningful differences were identified between undoped and highly doped PEDOT, with the optimized force fields capturing the finite size of charge carriers in doped PEDOT models.
Article
Biochemistry & Molecular Biology
Jiachen Li, Qi Wang, Yaoquan Tu
Summary: In this study, an advanced sampling technique was used to investigate the role of cleavage site sequences in prothrombin activation. The results suggest that the cleavage site at R320 is favored for prothrombin activation, and the binding between Pep320 and the FXa catalytic triad is more stable due to strong electrostatic interactions.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2022)
Review
Chemistry, Multidisciplinary
Danilo Milardi, Ehud Gazit, Sheena E. Radford, Yong Xu, Rodrigo U. Gallardo, Amedeo Caflisch, Gunilla T. Westermark, Per Westermark, Carmelo La Rosa, Ayyalusamy Ramamoorthy
Summary: The possible link between hIAPP accumulation and beta-cell death in diabetic patients has sparked a lot of research on amyloid structures and aggregation pathways. Recent studies have highlighted the importance of early oligomeric intermediates and their interactions with lipid membranes, pH, insulin, and zinc in the mechanism of hIAPP aggregation. Challenges in characterizing the aggregation process have led to the development of various biophysical and chemical approaches, with studies suggesting that restoring hIAPP proteostasis could be a promising strategy for therapy.
Article
Biochemistry & Molecular Biology
Sara Garcia-Vinuales, Michele F. M. Sciacca, Valeria Lanza, Anna Maria Santoro, Giulia Grasso, Grazia R. Tundo, Diego Sbardella, Massimiliano Coletta, Giuseppe Grasso, Carmelo La Rosa, Danilo Milardi
Summary: Alzheimer's Disease (AD) is characterized by amyloid deposits in the brain, with factors such as genetic background, other diseases, and lifestyle contributing to its development. Recent studies suggest a link between impaired lipid metabolism and A beta deposition, with membrane-bound A beta assemblies playing a key role in neurotoxicity. Additionally, dysregulation of lipid levels and toxic A beta aggregation may be linked to derangements in cellular pathways such as ubiquitin proteasome and autophagy. Understanding the role of lipids in A beta aggregation and proteostasis could lead to valuable treatment options.
CHEMISTRY AND PHYSICS OF LIPIDS
(2021)
Article
Chemistry, Physical
Cristina Cantarutti, Yamanappa Hunashal, Carmelo La Rosa, Marcello Condorelli, Sofia Giorgetti, Vittorio Bellotti, Federico Fogolari, Gennaro Esposito
Summary: It has been discovered that changing the ionic strength of the medium can adjust the form and strength of the interaction between nanoparticles and proteins, thus impacting the mechanism of nanomaterials on proteins.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2022)
Article
Biochemistry & Molecular Biology
Grazia Raffaella Tundo, Diego Sbardella, Francesco Oddone, Giuseppe Grasso, Stefano Marini, Maria Grazia Atzori, Anna Maria Santoro, Danilo Milardi, Francesco Bellia, Gabriele Macari, Grazia Graziani, Fabio Polticelli, Paolo Cascio, Mariacristina Parravano, Massimo Coletta
Summary: Carfilzomib has been found to target Insulin-Degrading Enzyme (IDE) in vitro, which has interactions with proteasomes in cells. The inhibitory effect of Carfilzomib on IDE is 10-fold lower than on 20S proteasomes. Additionally, the interaction of IDE with 20S enhances the inhibitory power of Carfilzomib on proteasomes. Silencing the IDE gene significantly reduces the cytotoxicity of Carfilzomib in rMC1 cells.
Article
Multidisciplinary Sciences
Hanna Korolainen, Fabio Lolicato, Giray Enkavi, Jesus Perez-Gil, Waldemar Kulig, Ilpo Vattulainen
Summary: This study investigated the details of SP-C dimerization using molecular dynamics simulations. The results revealed that SP-C dimerizes in pulmonary surfactant membranes and forms dimers with different topologies. These findings provide a stronger basis for understanding how SP-C functions together with other surfactant proteins.
Article
Biochemistry & Molecular Biology
Marco Persico, Anna Maria Santoro, Alessandro D'Urso, Danilo Milardi, Roberto Purrello, Alessandra Cunsolo, Marina Gobbo, Roberto Fattorusso, Donatella Diana, Manuela Stefanelli, Grazia R. Tundo, Diego Sbardella, Massimo Coletta, Caterina Fattorusso
Summary: Cationic porphyrins are versatile inhibitors that can bind to specific sites on the proteasome to inhibit its function. This study explores the interaction behavior of different structural porphyrin derivatives on 20S proteasome and evaluates their potential biological effects on breast cancer cells.
Article
Cell Biology
Fabio Lolicato, Roberto Saleppico, Alessandra Griffo, Annalena Meyer, Federica Scollo, Bianca Pokrandt, Hans-Michael Muller, Helge Ewers, Hendrik Hahl, Jean-Baptiste Fleury, Ralf Seemann, Martin Hof, Britta Brugger, Karin Jacobs, Ilpo Vattulainen, Walter Nickel
Summary: This study found that cholesterol can promote the recruitment and translocation of FGF2 in cells, as well as enhance its binding to PI(4,5)P2. Through molecular dynamics simulations and experiments, it was revealed that cholesterol modulates the binding of FGF2 to PI(4,5)P2 by increasing the visibility of PI(4,5)P2 on the membrane surface, inducing the clustering of PI(4,5)P2 molecules, and increasing membrane tension.
JOURNAL OF CELL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Carola Rando, Giuseppe Grasso, Dibakar Sarkar, Michele Francesco Maria Sciacca, Lorena Maria Cucci, Alessia Cosentino, Giuseppe Forte, Martina Pannuzzo, Cristina Satriano, Anirban Bhunia, Carmelo La Rosa
Summary: The role of hydrogen bonding in the stability of ion-channel-like pores formed by pentapeptides containing a GXXXG motif was investigated. Molecular dynamics simulations, quantum mechanics, and experimental biophysical techniques revealed that the stability of the pores is maintained by a C alpha-H...O hydrogen bond formed between a glycine in the GXXXG sequence and another amino acid in a neighboring α-helix.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Microbiology
Steffen Klein, Gonen Golani, Fabio Lolicato, Carmen Lahr, Daniel Beyer, Alexia Herrmann, Moritz Wachsmuth-Melm, Nina Reddmann, Romy Brecht, Mehdi Hosseinzadeh, Androniki Kolovou, Jana Makroczyova, Sarah Peterl, Martin Schorb, Yannick Schwab, Britta Bruegger, Walter Nickel, Ulrich S. Schwarz, Petr Chlanda
Summary: Interferon-induced transmembrane protein 3 (IFITM3) inhibits virus entry through lipid sorting to stabilize hemifusion and prevent fusion pore formation, ultimately leading to viral degradation in lysosomes. In situ cryo-electron tomography confirms the arrest of viral membrane fusion by IFITM3 and identifies hemifusion stabilization as the molecular mechanism. The presence of post-fusion conformation of the influenza fusion protein hemagglutinin near hemifusion sites further suggests that IFITM3 does not interfere with viral fusion machinery.
CELL HOST & MICROBE
(2023)
Article
Chemistry, Medicinal
Roberta Panebianco, Maurizio Viale, Fabrizio Loiacono, Valeria Lanza, Danilo Milardi, Graziella Vecchio
Summary: Metal terpyridine complexes have attracted significant interest in various fields, and the biological activity of terpyridine and its metal complexes has received considerable attention. To improve their water solubility and target them in cancer cells, we synthesized new terpyridine derivatives of trehalose and glucose. The glucose derivative and its copper(II) and iron(II) complexes exhibited antiproliferative activity, while the trehalose residue reduced the cytotoxicity. Additionally, we evaluated the ability of the parent terpyridine ligands and their copper complexes to inhibit proteasome activity as an antineoplastic mechanism.
Article
Biochemistry & Molecular Biology
Sophie L. Winter, Gonen Golani, Fabio Lolicato, Melina Vallbracht, Keerthihan Thiyagarajah, Samy Sid Ahmed, Christian Luechtenborg, Oliver T. Fackler, Britta Bruegger, Thomas Hoenen, Walter Nickel, Ulrich S. Schwarz, Petr Chlanda
Summary: During Ebola virus entry into host cells, the virus disassembles and releases the nucleocapsid into the cytosol. This process is driven by the weakening of viral protein 40 (VP40) interactions caused by low endosomal pH. The disassembly of VP40 acts as a molecular switch coupling viral matrix uncoating to membrane fusion.
Article
Biochemistry & Molecular Biology
Alessandro D'Urso, Roberto Purrello, Alessandra Cunsolo, Danilo Milardi, Caterina Fattorusso, Marco Persico, Maria Gaczynska, Pawel A. Osmulski, Anna Maria Santoro
Summary: Many chronic diseases, including cancer and neurodegeneration, are associated with proteasome dysregulation. The proteasome activity plays a crucial role in maintaining cellular proteostasis and is controlled by the gating mechanism and its conformational transitions. This study suggests that electronic circular dichroism (ECD) can be used as a convenient method to monitor proteasome conformational changes related to gating phenomena.
Article
Biology
Thomas Kupke, Rabea M. Goetz, Florian M. Richter, Rainer Beck, Fabio Lolicato, Walter Nickel, Carsten Hopf, Britta Bruegger
Summary: The article introduces a simple assay, iCLiPSpy, for studying intramembrane-cleaving proteases (I-CLiPs) in vivo. This method allows for easy detection of enzyme activity and investigation of residues important for substrate binding and activity. It has the potential to be used as a screening assay for I-CLiP inhibitors or activators.
COMMUNICATIONS BIOLOGY
(2023)
Article
Chemistry, Inorganic & Nuclear
Vincenzo Mangini, Giulia Grasso, Benny Danilo Belviso, Michele F. M. Sciacca, Valeria Lanza, Rocco Caliandro, Danilo Milardi
Summary: The study reveals that copper and zinc ions have an impact on the stability and structure of polyubiquitin chains, with copper ions leading to protein destabilization and dimer aggregation, and zinc ions having a more significant effect on protein structure and dynamics. This study enhances our understanding of Ub chain recognition mechanisms and highlights the potential of targeting metal-mediated disruptions in Ub signaling for treating diseases associated with abnormal protein accumulation.
DALTON TRANSACTIONS
(2023)
Article
Chemistry, Medicinal
Shuang Mei, Su Jiang, Yuting Wang, Han Jing, Peng Yang, Miao-Miao Niu, Jindong Li, Kai Yuan, Yan Zhang
Summary: This study identifies a dual-targeting peptide, AP-1, that effectively inhibits variants of concern (VOCs) of SARS-CoV-2 without impairing host cell viability. The findings suggest that AP-1 could be a promising broad-spectrum agent for treating emerging VOCs of SARS-CoV-2.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Hyeonjun Lee, Ju Yeon Lee, Hyunsoo Jang, Hye Young Cho, Minhee Kang, Sang Hyun Bae, Suin Kim, Eunji Kim, Jaebong Jang, Jin Young Kim, Young Ho Jeon
Summary: By using liquid chromatography-tandem mass spectrometry and nuclear magnetic resonance experiments, we identified new chemical moieties that bind to the target sites of the protein of interest, allowing for reversible binding and protein degradation. This method has the potential to expand the application of PROTAC technology.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Yingying Li, Xiyou Du, Xinru Kong, Yuelin Fang, Zhijing He, Dongzhu Liu, Hang Wu, Jianbo Ji, Xiaoye Yang, Lei Ye, Guangxi Zhai
Summary: This study proposes a novel nanoplatform based on the autophagy cascade to overcome the obstacles in chemo-immunotherapy. The platform combines chemotherapy and starvation therapy to initiate pro-death autophagy and enhance antigen presentation, while also remodeling the immunosuppressive tumor microenvironment. Furthermore, the study discovers a new therapeutic direction for the respiration inhibitor 3-bromopyruvic acid (3BP) in cancer treatment. Overall, this study offers an opportunity to improve antitumor efficacy and boost immune responses.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Bingsi Wang, Mingxu Ma, Yusen Dai, Pengfei Yu, Liang Ye, Wenyan Wang, Chunjie Sha, Huijie Yang, Yingjie Yang, Yunjing Zhu, Lin Dong, Shujuan Wei, Linlin Wang, Jingwei Tian, Hongbo Wang
Summary: Breast cancer is a common malignant tumor in women, and drug resistance remains a clinical challenge. In this study, a novel compound, G-5b, was developed with potent antagonistic and degradation activities comparable to the current drug fulvestrant. G-5b also showed improved stability and solubility. Mechanistically, G-5b engages the proteasome pathway to degrade ER, inhibiting the ER signaling pathway and inducing apoptosis and cell cycle arrest. In animal models, G-5b exhibited superior pharmacokinetics and pharmacodynamics properties. Overall, G-5b is a promising long-acting SERD worthy of further investigation and optimization.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Karoline B. Waitman, Larissa C. de Almeida, Marina C. Primi, Jorge A. E. G. Carlos, Claudia Ruiz, Thales Kronenberger, Stefan Laufer, Marcia Ines Goettert, Antti Poso, Sandra V. Vassiliades, Vinicius A. M. de Souza, Monica F. Z. J. Toledo, Neuza M. A. Hassimotto, Michael D. Cameron, Thomas D. Bannister, Leticia Costa-Lotufo, Joa o A. Machado-Neto, Mauricio T. Tavares, Roberto Parise-Filho
Summary: A series of hybrid inhibitors combining pharmacophores of known kinase inhibitors and benzohydroxamate HDAC inhibitors were synthesized and evaluated for their anticancer activity and pharmacokinetic properties. Compounds 4d-f exhibited promising cytotoxicity against hematological cells and moderate activity against solid tumor models. Compound 4d showed potent inhibition of multiple kinase targets and had stable interactions with HDAC and members of the JAK family. These compounds showed selective cytotoxicity with minimal effects on non-tumorigenic cells and favorable pharmacokinetic profiles.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Michal Sulik, Diana Fontinha, Dietmar Steverding, Szymon Sobczak, Michal Antoszczak, Miguel Prudencio, Adam Huczynski
Summary: This study describes the synthesis of the first-in-class ivermectin derivatives obtained through derivatization of the C13 position, along with the unexpected rearrangement of the macrolide ring. These derivatives show potential for antiparasitic activity and are important for the development of new antiparasitic agents.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Jun Liu, Qiu-Xian Chen, Wen-Fu Wu, Dong Wang, Si -Yu Zhao, Jia-Hao Li, Yi-Qun Chang, Shao-Gao Zeng, Jia-Yi Hu, Yu-Jie Li, Jia-Xin Du, Shu-Meng Jiao, Hai-Chuan Xiao, Qiang Zhang, Jun Xu, Jian-Fu Zhao, Hai -Bo Zhou, Yong-Heng Wang, Jian Zou, Ping-Hua Sun
Summary: A new anti-infective drug strategy has been discovered to attenuate virulence and modulate inflammation caused by drug-resistant Pseudomonas aeruginosa infections. Compound 5f inhibits biofilm formation, macrophage migration, and inflammatory response induced by P. aeruginosa, showing potential as a novel candidate against drug-resistant infections.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Liuzeng Chen, Ke Wang, Lingyun Wang, Wei Wang, Lifan Wang, Jia Li, Xiaohan Liu, Mengya Wang, Banfeng Ruan
Summary: In this study, a series of novel anti-inflammatory compounds were designed and synthesized based on the natural product pterostilbene skeleton. Among them, compound 8 showed the highest activity and exhibited its effects through inhibition of pro-inflammatory cytokines by blocking the NF-KB/MAPK signaling pathway. Compound 8 also demonstrated a good relieving effect on acute colitis in mice and showed good safety in acute toxicity experiments.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Si-Min Liang, Gui-Bin Liang, Hui-Ling Wang, Hong Jiang, Xian-Li Ma, Jian-Hua Wei, Ri-Zhen Huang, Ye Zhang
Summary: A series of novel multi-target antitumor agents were designed, synthesized, and evaluated. Some compounds exhibited significant antitumor activity and one compound showed excellent efficacy, limited toxicity, and low resistance. Further mechanism studies revealed that the compound exerted antitumor effects through multiple pathways.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
