Editorial Material
Chemistry, Medicinal
Mark Klein
Summary: Cyclin-dependent kinases (CDKs) have important roles in normal cells and can be targeted for cancer therapy. CDK4 inhibitors have been approved for advanced breast cancer treatment. However, the development of selective inhibitors for individual CDKs is challenging due to the highly conserved ATP-binding site.
Article
Pharmacology & Pharmacy
Yanting Zhou, Xiandeng Li, Peifang Luo, Huiting Chen, Yan Zhou, Xueting Zheng, Yuan Yin, Haoche Wei, Hongji Liu, Wen Xia, Mingsong Shi, Xiaoan Li
Summary: CDK4/6 is a crucial player in various cancers and a potential target for anticancer drugs. The interaction between abemaciclib and human CDK6 was studied, and C2231-A was identified as a promising candidate compound with significant inhibitory effects on human breast cancer cell lines.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Rashid Waseem, Saleha Anwar, Shama Khan, Anas Shamsi, Md. Imtaiyaz Hassan, Farah Anjum, Alaa Shafie, Asimul Islam, Dharmendra Kumar Yadav
Summary: The study demonstrates that irisin binds to MARK4 and inhibits its activity, providing a new therapeutic approach for MARK4-associated diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Haiyan Jin, Jongwan Kim, Onju Lee, Hyein Kim, Kyoung Tai No
Summary: In this study, we used the fragment molecular orbital (FMO) method to explore the molecular mechanisms of small-molecule inhibitors binding to PLK1. The findings provide valuable insights for designing potent and selective PLK1 inhibitors, which can have significant implications for developing anti-cancer therapeutics.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Rosario Tomarchio, Vincenzo Patamia, Chiara Zagni, Letizia Crocetti, Agostino Cilibrizzi, Giuseppe Floresta, Antonio Rescifina
Summary: Ordinary small molecule de novo drug design is time-consuming and expensive. Computational tools, such as molecular dynamics (MD) simulations and steered molecular dynamics (SMD), have shown promise in accelerating the drug design process. In this paper, we applied SMD to evaluate the binding properties of small molecules with FABP4, which is of interest for inhibiting FABP4 and has therapeutic potential in treating cancer and other diseases.
Article
Biochemistry & Molecular Biology
Ognjen Perisic, Willy Wriggers
Summary: The study utilized mutual information (MI) analysis to explore the mechanical resistance of the Top7 protein, providing a global overview of perturbation effects and proposing a novel mutation design based on residue hydropathy. The combination of MI analysis with conventional trajectory analysis offers valuable insights for engineering more resistant protein mutants without introducing covalent crosslinks, potentially preserving the protein's conformational space and unfolding pathway.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Victor Vasquez-Montes, Vivek Tyagi, Eden Sikorski, Alexander Kyrychenko, J. Alfredo Freites, Damien Thevenin, Douglas J. Tobias, Alexey S. Ladokhin
Summary: The study investigates the effects of PS, Ca2+, and peptide protonation state on the interactions of pHLIP with lipid membranes. Cellular experiments demonstrate that exposed PS on the plasma membrane promotes pHLIP targeting and the magnitude of this effect depends on extracellular Ca2+ concentration. The mechanism of targeting is further explored through a combination of fluorescence and molecular dynamics simulations.
Article
Neurosciences
Xingfeng Xu, Mao Li, Yan Su, Qi Wang, Peifang Qin, Haitao Huang, Yuting Zhang, Yali Zhou, Jianguo Yan
Summary: This article aimed to explore the potential mechanism of C9orf72 involved in the pathogenesis of Parkinson's disease (PD). The study found that the expression level of C9orf72 protein was significantly reduced in PD models, while the mRNA expression level remains unchanged. The degradation of C9orf72 protein was mainly through the ubiquitin-proteasome pathway, and its phosphorylation at the S9 site promoted its degradation. Knockdown of C9orf72 aggravated autophagy dysfunction and increased neuronal loss and motor dysfunction in PD mice, while overexpression of C9orf72 alleviated autophagy dysfunction in PD neurons. Interfering with Cdk5 phosphorylation at the S9 site of C9orf72 could alleviate autophagy dysfunction, neuronal death, and motor dysfunction caused by C9orf72 protein degradation.
CNS NEUROSCIENCE & THERAPEUTICS
(2023)
Article
Automation & Control Systems
Guanxing Chen, Haohuai He, Lu Zhao, Kuen-Bao Chen, Siyuan Li, Calvin Yu-Chian Chen
Summary: Recent research has identified CDK7, CDK9, and CCNT1 as players in transcriptional misregulation in cancer. Using a combination of traditional virtual screening and artificial intelligence models, we identified potential multi-target inhibitors from the FDA database. Our results showed that Adaptive Boosting-Decision Tree Regression (AdaBoost), Support Vector Machine Regression (SVR), and Ridge Regression (Ridge) achieved good results in predicting CDK7 inhibitors, while AdaBoost, Random Forest (RF), and Ridge performed well for CDK9 inhibitors. Based on molecular dynamics simulations and analysis, we propose two potential multi-target inhibitors for TNBC.
CHEMOMETRICS AND INTELLIGENT LABORATORY SYSTEMS
(2022)
Article
Polymer Science
Ran Chen, Chuanfu Luo
Summary: This study investigates the effect of stretching on the intrachain conformational ordering of PE, iPP, and iPB-1 single chains using all-atom steered molecular dynamics simulations. The results show that proper stretching can promote the formation of helical structures in iPP and iPB-1 chains. However, excessive force can lead to the instability and destruction of helices. The end-to-end distance of chains is suggested as a controlling factor for helix formation.
Article
Microbiology
Juri Kim, Eun-Ah Park, Mee Young Shin, Soon-Jung Park
Summary: This study investigated the functional roles of Giardia lamblia CDKs (GlCDKs) and their cognate cyclins. Using morpholino-mediated knockdown and coimmunoprecipitation, the functions of GlCDK1 and GlCDK2 were distinguished. GlCDK1 with Glcyclin 3977 plays a crucial role in flagellum formation and cell cycle control of G. lamblia, while GlCDK2 with Glcyclin 22394/6584 is involved in cell cycle control.
MICROBIOLOGY SPECTRUM
(2023)
Review
Biochemistry & Molecular Biology
Pawel Lukasik, Michal Zaluski, Izabela Gutowska
Summary: Cyclin-dependent kinases are crucial in various cellular processes and their dysregulation can lead to diseases, making them potential drug targets.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Multidisciplinary
Lyman Monroe, Daisuke Kihara
Summary: The stability of protein structures can be measured by AFM pulling experiments, and this study used computational pulling to estimate the accuracy of protein structure models. It was found that near-native models can be selected by examining the break forces, indicating that high break force indicates high stability of models.
JOURNAL OF COMPUTATIONAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Amit Kumawat, Sadanandam Namsani, Debabrata Pramanik, Sudip Roy, Jayant K. Singh
Summary: The research focuses on drug repurposing strategies against coronavirus infection by targeting host proteins involved in viral replication and disease progression. Through high throughput analysis and molecular docking, potential drug candidates for COVID-19 treatment have been identified, along with chemical compounds that bind to gene transcription and translation regulatory proteins with higher affinity. The study also highlights the growing interest in combination therapy targeting multiple enzymes/pathways.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Biochemistry & Molecular Biology
Susan Kelso, Siobhan O'Brien, Igor Kurinov, Stephane Angers, Frank Sicheri
Summary: CDK11 is a kinase that controls cell proliferation by regulating transcription, RNA splicing, and the cell cycle. OTS964 is a small-molecule inhibitor that shows specificity for CDK11 in cells. The crystal structure analysis reveals that CDK11 adopts an active-like conformation when bound to OTS964. The contribution of specific amino acids to the binding of OTS964 to CDK11 was evaluated by in vitro isothermal titration calorimetry (ITC) and resistance studies in cells.
Article
Polymer Science
Jia Long Liu, Lorenzo Mencattelli, Jie Zhi, Ping Yee Chua, Tong-Earn Tay, Vincent Beng Chye Tan
Summary: This study presents a novel structure for glass-fiber-reinforced polymer (GFRP) laminates, which significantly improves their impact performance and fiber damage resistance. Compared to conventional laminates, this structure is lighter and effectively reduces fiber damage.
Article
Engineering, Multidisciplinary
Ashish Kumar Singh, Vincent B. C. Tan, Tong Earn Tay, Heow Pueh Lee
Summary: This paper presents a numerical study of the nonlinear vibro-ultrasonic behavior of a composite laminate with delamination defects. It introduces a methodology to model laminates and proposes a new approach called the surface vibration comparison method for non-contact detection of delamination defects.
JOURNAL OF NONDESTRUCTIVE EVALUATION, DIAGNOSTICS AND PROGNOSTICS OF ENGINEERING SYSTEMS
(2022)
Article
Mechanics
Mohammad S. Rouhi, Dimitra Ramantani, Tong Earn Tay
Summary: This research paper presents an experimental test setup and a 3D physically-based progressive damage model to predict the failure load of hybrid bolted joints between composite materials and metals. The study shows that numerical models can be used to aid in the design of stiffness and strength in bolted joints.
COMPOSITE STRUCTURES
(2022)
Article
Engineering, Manufacturing
J. L. Liu, Z. A. B. Mazeli, T. E. Tay, V. B. C. Tan
Summary: Bio-inspired helicoidal CFRP laminates can sustain higher loads and be effectively healed after impact using thermoplastic laminates. Ply blocking improves ply toughness and healing efficiency.
COMPOSITES PART A-APPLIED SCIENCE AND MANUFACTURING
(2022)
Article
Engineering, Manufacturing
K. H. Leong, J. Zhi, H. P. Lee, V. B. C. Tan, T. E. Tay
Summary: This paper proposes an adaptive multi-fidelity (AMF) modelling approach that combines high-fidelity 3D elements with discrete cracks for actively damaging areas, and lower-fidelity shell elements with smeared cracks for dormant and inactive sites. The transition criteria between these levels of modelling are studied to balance fidelity to physics with computational efficiency. Results are benchmarked against high-fidelity simulations and experimental data, showing accurate modeling of progressive failure in composite laminates.
COMPOSITES PART A-APPLIED SCIENCE AND MANUFACTURING
(2022)
Article
Engineering, Multidisciplinary
Jie Zhi, Leong Hien Poh, Tong-Earn Tay, Vincent Beng Chye Tan
Summary: This paper presents a concurrent multilevel modeling approach called Direct FE2, which connects the macroscopic and microscopic behaviors of materials and allows for accurate prediction of deformation in composite materials.
COMPUTER METHODS IN APPLIED MECHANICS AND ENGINEERING
(2022)
Article
Materials Science, Composites
Mohammad S. Rouhi, J. L. Liu, M. Ridhwan Bin Hamzah, Vincent B. C. Tan, Tong-Earn Tay
Summary: This work focuses on developing a seamlessly integrated modeling platform for manufacturing, designing, and analyzing fiber-reinforced composite structures. The unique integration of two commercial software with physics-based micromechanics enables the direct embedding of variabilities during the manufacturing into the structural analysis, allowing for seamless transfer of process effects and properties variability to the final structural analysis.
JOURNAL OF REINFORCED PLASTICS AND COMPOSITES
(2023)
Article
Chemistry, Physical
Jiaqin Wang, Vincent B. C. Tan
Summary: The study suggests that stress concentrations around inherent defects in materials can sometimes be reduced by adding nanoparticles to improve material strength. However, experiments coating nanoinclusions with a layer of rubbery material aiming for higher energy absorption did not computationally achieve the expected strength enhancement.
Article
Mechanics
K. H. Leong, J. Zhi, H. P. Lee, V. B. C. Tan, T. E. Tay
Summary: In this paper, an adaptive multi-fidelity (AMF) approach is proposed to model progressive damage in composite laminates under bending load. The AMF method has been previously validated in the analysis of open hole tensile problems. This study extends the application of AMF to predict delamination migration and demonstrates its accuracy in different loading conditions.
COMPOSITE STRUCTURES
(2023)
Article
Engineering, Multidisciplinary
Jie Zhi, Karh Heng Leong, Kirk Ming Yeoh, Tong -Earn Tay, Vincent Beng Chye Tan
Summary: A multiscale method is proposed in this study to model thin-walled fiber reinforced composite laminates using Mindlin-Reissner shell theory and Direct FE2. The method employs a first-order homogenization framework to handle the scale transitions and considers in-plane and through-thickness periodicity. It avoids the upscaling of macroscopic stresses and tangents in the conventional nested FE2 scheme, making it useful for modeling damage propagation in composite structures.
COMPUTER METHODS IN APPLIED MECHANICS AND ENGINEERING
(2023)
Article
Mathematics
Ang Zhao, Vincent Beng Chye Tan, Pei Li, Kui Liu, Zhendong Hu
Summary: This paper proposes a filtering-based reconstruction method to solve the checkerboard problem and provides an important solution for the practical application of multiscale topology optimization.
Article
Materials Science, Composites
Kirk Ming Yeoh, Leong Hien Poh, Tong-Earn Tay, Vincent Beng Chye Tan
Summary: In finite element analyses, composite laminates are often homogenised and modelled using beam and plate elements. However, these structural elements are inaccurate for laminates with distinct in-plane stiffnesses, such as sandwich structured composites. To address this issue, a multiscale layerwise beam model based on the Timoshenko-Ehrenfest beam theory is proposed, which captures the key deformation modes of bending and transverse shear. The model is implemented using Direct FE2, a versatile computational homogenisation scheme that also captures deformation mechanisms at the mesoscale. The proposed approach provides accurate macroscale responses and resolution to mesoscale deformations in significantly less computation time.
COMPOSITES SCIENCE AND TECHNOLOGY
(2023)
