Article
Chemistry, Physical
Arthur Voronin, Alexander Schug
Summary: Despite significant progress in experimental techniques, protein structure determination remains a challenging task. Computer simulations are often used to complement or interpret experimental data, with many methods providing highly accurate protein structure models. Research focuses on selecting representative members or ensembles from computationally generated structures.
JOURNAL OF CHEMICAL PHYSICS
(2022)
Article
Chemistry, Multidisciplinary
Xian-Yang Zhou, Ling-Xin Li, Zhen Zhang, Shi-Chao Duan, Ying-Wen Huang, Yi-Yang Luo, Xiao-Dong Mu, Zhi-Wei Chen, Yong Qin, Jing Hu, Jian Yin, Jin-Song Yang
Summary: Acinetobacter baumannii poses a serious threat to global health, and its lipopolysaccharide (LPS) has been found to have antigenic properties. Research has identified a potential antigenic epitope in one of the branches of the LPS, which is attractive for the development of carbohydrate vaccines against A. baumannii.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Biochemistry & Molecular Biology
Weiping Lyu, Qihang Li, Yingming Wang, Chenxi Du, Feng Feng, Heng Chi, Yuan Li, Wenyuan Liu, Haopeng Sun
Summary: Cellular autophagy is an intracellular degradation pathway that maintains cell homeostasis, and dysfunctions in autophagy are closely related to various diseases. The protein-protein interaction between LC3 and p62 plays a critical role in autophagosome formation, yet research on inhibitors targeting this interaction is still lacking.
BIOORGANIC CHEMISTRY
(2021)
Article
Chemistry, Physical
Samuel D. Winter, Hannah B. L. Jones, Dora M. Rasadean, Rory M. Crean, Michael J. Danson, G. Dan Panto, Gergely Katona, Erica Prentice, Vickery L. Arcus, Marc W. van der Kamp, Christopher R. Pudney
Summary: This study investigates how individual substrate interactions affect the temperature dependence of enzyme activity and the network of motions throughout the protein, revealing how subtle changes in substrate binding can affect global changes in motion and flexibility extending throughout the protein.
Article
Biochemistry & Molecular Biology
Alexander Zhuravlev, Alejandro Cruz, Vladislav Aksenov, Alexey Golovanov, Jose M. Lluch, Hartmut Kuhn, Angels Gonzalez-Lafont, Igor Ivanov
Summary: This study investigates the functionality of ALOX15 in different cancer and inflammation models, and suggests that certain derivatives can inhibit its catalytic activity. Through computational simulations, the researchers identified a common pharmacophore that is critical for this allosteric inhibition.
Review
Biochemistry & Molecular Biology
Alessandro Berselli, Fabio Benfenati, Luca Maragliano, Giulio Alberini
Summary: Claudins (Cldns) are transmembrane proteins that play a major role in tight junction integrity and tissue selectivity. Computational methodologies have been used to investigate the properties of Cldn and provide valuable insights for improving the characterization of Cldn and designing strategies for controlling paracellular transport.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Alessandro Berselli, Fabio Benfenati, Luca Maragliano, Giulio Alberini
Summary: Claudins are transmembrane proteins that play a crucial role in tight junction integrity and tissue selectivity. They form barriers or ion-selective channels between cells in the paracellular space. Computational methodologies have helped to elucidate the properties of Claudins and could be useful for designing strategies to control the transport of drugs or molecules.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2022)
Review
Chemistry, Multidisciplinary
Omer Harel, Muhammad Jbara
Summary: Nature has developed a variety of protein machinery to regulate cellular processes. Post-expression modifications play a crucial role in modulating protein synthesis, folding, and activation. Synthetic chemistry has contributed significantly to protein science by allowing the preparation of bioactive proteins with novel properties for biomedical research and applications.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Multidisciplinary Sciences
Zhenzhen Wang, Xiaoqing Hu, Xiaorui Xue, Shengpeng Zhou, Xiaokai Li, Yizhang Yang, Jiaqi Zhou, Zheng Shu, Banchi Zhao, Xitao Yu, Maomao Gong, Zhenpeng Wang, Pan Ma, Yong Wu, Xiangjun Chen, Jianguo Wang, Xueguang Ren, Chuncheng Wang, Dajun Ding
Summary: By developing a laser-induced electron recollision-assisted Coulomb explosion imaging approach and molecular dynamics simulations, the authors captured snapshots of the vibrational wave-packets of the excited and ground states of D2O+ simultaneously with sub-10 picometre and few-femtosecond precision. These results provide comprehensive structural information for studying the fascinating molecular dynamics of water, and pave the way towards making a movie of excited state-resolved ultrafast molecular dynamics and light-induced chemical reaction.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Dusan S. Dimic, Goran N. Kaluderovic, Edina H. Avdovic, Dejan A. Milenkovic, Marko N. Zivanovic, Ivan Potocnak, Erika Samolova, Milena S. Dimitrijevic, Luciano Saso, Zoran S. Markovic, Jasmina M. Dimitric Markovic
Summary: In this study, four new compounds synthesized from 4-hydroxycoumarin and tyramine/octopamine/norepinephrine/3-methoxytyramine were characterized and analyzed spectroscopically, chromatographically, and structurally. The stability, antitumor activity, and ecotoxicology of these compounds were investigated using experimental and computational methods.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Arman Abdalla Ali, Shakhawan Ahmad Mhamad, Aso Hameed Hasan, Iqrar Ahmad, Siti Awanis Abdullah, Shajarahtunnur Jamil, Harun Patel, Sankaranarayanan Murugesan, Joazaizulfazli Jamalis
Summary: Acetylcholinesterase inhibitors (AChEIs) have been investigated for the treatment of Alzheimer's disease. This study focused on synthesizing chalcone derivatives with anti-cholinesterase potential. The compounds exhibited potent inhibitory activity against AChE, with compound 11i showing the most potent activity compared to the positive compound, Galantamine. Docking studies and molecular dynamics simulation confirmed the significant binding affinity and stability of compound 11i in the acetylcholinesterase enzyme.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Cell Biology
Ziyang Shan, Xuemei Yang, Huihui Liu, Yafei Yuan, Yuan Xiao, Jing Nan, Wei Zhang, Wenqi Song, Jufang Wang, Feiwen Wei, Yanqing Zhang
Summary: Members of the OATPs family transport a wide range of organic anions, including drugs and metabolites, into the liver. OATP1B1, an important member of this family, is responsible for the hepatic clearance of various substances. In this study, cryo-EM structures of human OATP1B1 in different states were determined, providing insights into its transport mechanism and potential drug-drug interactions.
Article
Biochemistry & Molecular Biology
Olivia Love, Maria Carolina Pacheco Lima, Casey Clark, Sean Cornillie, Shelly Roalstad, Thomas E. Cheatham
Summary: Flexible loop regions of proteins play critical roles in biological processes and accurate sampling of their 3D structures is vital for drug design and molecular system knowledge. Experimental techniques may not provide high-resolution information for flexible loop domains due to their complex and dynamic nature. In silico methods using molecular dynamics can overcome this limitation. This study evaluates the ability of the AMBER protein force field to model the conformations of dihydrofolate reductase (DHFR), a protein complex with flexible loops whose conformations depend on the presence of ligands and cofactors. Results suggest that the AMBER force field may not accurately sample the expected loop conformations, indicating a potential imbalance in the available force field parameters.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Energy & Fuels
Ali Ghamartale, Nima Rezaei, Sohrab Zendehboudi
Summary: Asphaltene deposition is a challenge in petroleum production and chemical inhibitors are commonly used to mitigate it. This study used molecular dynamics simulation to investigate the impact of chemical inhibitors on the binding arrangement of two asphaltene structures. The results showed that organic sulfuric acid and ionic liquids can interfere with asphaltene aggregation.
Article
Engineering, Chemical
Simona Dobrinas, Alina Soceanu, Semaghiul Birghila, Corina Birghila, Nicoleta Matei, Viorica Popescu, Luminita Mihaela Constanda
Summary: "This study evaluates the quality of bee honey from different sources through sensory analysis and chemical testing. The results show that the honey samples meet the quality regulations for commercial products. The observed variations can be attributed to the difference in plant species, harvesting period, and environmental pollutants. The study also identifies correlations between physico-chemical parameters and metal content."
Article
Chemistry, Medicinal
Khuchtumur Bum-Erdene, Mona K. Ghozayel, David Xu, Samy O. Meroueh
Summary: This study discovered that covalent bond formation at Cys-284 of Rgl2 inhibits the activation of Ral GTPase. Chloroacetamide and acrylamide fragments were identified as potential inhibitors of Ral GTPase exchange by Rgl2. Indoline fragments were found to be the most promising series for further development.
Article
Biochemistry & Molecular Biology
Maria Raics, Alex Kalman Balogh, Chandan Kishor, Istvan Timari, Francisco J. Medrano, Antonio Romero, Rob Marc Go, Helen Blanchard, Laszlo Szilagyi, Katalin E. Kover, Krisztina Feher
Summary: In this study, the binding affinities of two selenium-containing hGal-3 inhibitors to hGal-3 were investigated using NMR spectroscopy and fluorescence anisotropy titrations. The results showed that these derivatives bind to hGal-3 at a specific site, but with weaker interaction strength.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Medicinal
Khuchtumur Bum-Erdene, Patrick M. Collins, Matthew W. Hugo, Somayeh S. Tarighat, Fei Fei, Chandan Kishor, Hakon Leffler, Ulf J. Nilsson, John Groffen, I. Darren Grice, Nora Heisterkamp, Helen Blanchard
Summary: In this study, novel Galectin-3 antagonists with enhanced affinity and selectivity were designed and synthesized. Experimental results demonstrated the specific inhibition of Galectin-3-induced BCP-ALL cell agglutination and decreased viability of ALL cells. Therefore, these compounds show promise as important leads for cancer therapeutics.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Immunology
Abdulraouf Ramadan, Zhiyi Cao, Mujtaba Hassan, Fredrik Zetterberg, Ulf J. Nilsson, Mihaela Gadjeva, Vijay Rathinam, Noorjahan Panjwani
Summary: In this study, researchers found that galectin-8 (Gal-8), a carbohydrate-binding protein, plays an important role in regulating the innate immune response to Pseudomonas aeruginosa keratitis. Gal-8-/- mice were resistant to the infection, while mice deficient in other galectins were susceptible. The addition of exogenous Gal-8 suppressed the activation of the TLR4 pathway and improved bacterial killing capacity by neutrophils. Moreover, injecting a Gal-8 inhibitor reduced the severity of infection in a mouse model. These findings have implications for developing new therapeutic strategies for conditions resulting from an overactive immune response.
JOURNAL OF IMMUNOLOGY
(2023)
Article
Chemistry, Medicinal
Khuchtumur Bum-Erdene, I-Ju Yeh, Giovanni Gonzalez-Gutierrez, Mona K. Ghozayel, Karen Pollok, Samy O. Meroueh
Summary: This study reports small molecules that can bind to TEAD and inhibit its binding to YAP/TAZ, thereby suppressing tumor growth and metastasis.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Cell Biology
Morten A. A. Nielsen, Ditte Koster, Akul Y. Y. Mehta, Kristian Stengaard-Pedersen, Pierre Busson, Peter Junker, Kim Horslev-Petersen, Merete Lund Hetland, Mikkel ostergaard, Malene Hvid, Hakon Leffler, Tue W. W. Kragstrup, Richard D. D. Cummings, Bent Deleuran
Summary: This study evaluated the clinical and pathogenic aspects of Gal-9 in rheumatoid arthritis (RA) and found that it plays a role in modulating synovial FLS activities and maintaining subclinical disease activity.
Article
Chemistry, Medicinal
Alexander D. D. Landgraf, I-Ju Yeh, Mona K. K. Ghozayel, Khuchtumur Bum-Erdene, Giovanni Gonzalez-Gutierrez, Samy O. O. Meroueh
Summary: In this study, we explored the deep pocket in the structure of Ral protein by designing and synthesizing several fragment derivatives. We successfully created two compounds, SOF-658 and SOF-648, which formed a strong adduct specifically at Tyr-82 in Ral protein, inhibiting its activity and blocking invasion of pancreatic ductal adenocarcinoma cancer cells.
Article
Chemistry, Medicinal
Mukul Mahanti, Kumar Bhaskar Pal, Rohit Kumar, Markus Schulze, Hakon Leffler, Derek T. Logan, Ulf J. Nilsson
Summary: The sulfur oxidation state of galactoside ligands affects the thermodynamics and structure of their interactions with galectin-3.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Robert J. Brenner, Alexander D. Landgraf, Khuchtumur Bum-Erdene, Giovanni Gonzalez-Gutierrez, Samy O. Meroueh
Summary: KRAS GTPases with oncogenic mutations are common in human tumors but are difficult to target with drugs due to the absence of suitable binding sites. In this study, a unique crystal structure of His-tagged KRAS(G12D) was reported, revealing a conformational change and an interface resembling high-affinity protein-protein complexes. Alanine-scanning and computational analysis identified key amino acids and druggable binding pockets at the interface. Small-molecule binding to these pockets could stabilize the inhibited structure and provide a new strategy to inhibit RAS signaling.
Article
Chemistry, Medicinal
Fredrik R. Zetterberg, Alison MacKinnon, Thomas Brimert, Lise Gravelle, Richard E. Johnsson, Barbro Kahl-Knutson, Hakon Leffler, Ulf J. Nilsson, Anders Pedersen, Kristoffer Peterson, James A. Roper, Hans Schambye, Robert J. Slack, Susan Tantawi
Summary: This study presents a series of selective galectin-3 inhibitors with high affinity and oral bioavailability. These compounds show antifibrotic activity in fibrosis-related diseases and one of them has been selected as a clinical candidate for further research.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Fredrik R. Zetterberg, Alison MacKinnon, Thomas Brimert, Lise Gravelle, Richard E. Johnsson, Barbro Kahl-Knutson, Hakon Leffler, Ulf J. Nilsson, Anders Pedersen, Kristoffer Peterson, James A. Roper, Hans Schambye, Robert J. Slack, Susan Tantawi
Summary: Galectin-3 is a crucial carbohydrate-binding protein involved in the regulation of various diseases. The discovery of GB0139, a high-affinity drug for idiopathic pulmonary fibrosis, has opened up new possibilities for treatment. By optimizing physical and chemical parameters, a series of highly selective galectin-3 inhibitors with both high affinity and oral bioavailability have been developed. These compounds have demonstrated anti-fibrotic activity in liver and lung fibrosis mouse models and show promising pharmacokinetic and safety profiles. GB1211 has been selected as a clinical candidate for liver cirrhosis and cancer, and phase IIa clinical trials are currently underway.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Education & Educational Research
Brooke Harris-Reeves, Andrew Pearson, Helen Massa
Summary: Successful transition for university students is crucial for their satisfaction and success. This study investigates the potential mismatch between students' expectations and their actual experiences. The findings highlight the importance of incorporating academic skill development and employability curricula and assessment in transition initiatives to support students' successful transition.
JOURNAL OF UNIVERSITY TEACHING AND LEARNING PRACTICE
(2022)