Article
Biochemistry & Molecular Biology
Soumyendu Sekhar Bandyopadhyay, Anup Kumar Halder, Monika Zareba-Koziol, Anna Bartkowiak-Kaczmarek, Aviinandaan Dutta, Piyali Chatterjee, Mita Nasipuri, Tomasz Wojtowicz, Jakub Wlodarczyk, Subhadip Basu
Summary: The study introduces a consensus strategy for predicting palmitoylated cysteine sites on synaptic proteins, which significantly improves prediction performance in mouse datasets through efficient feature selection and a three-star quality consensus strategy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Francisco S. Mesquita, Laurence Abrami, Lucie Bracq, Nattawadee Panyain, Vincent Mercier, Beatrice Kunz, Audrey Chuat, Joana Carlevaro-Fita, Didier Trono, F. Gisou van der Goot
Summary: This study found that SARS-CoV-2 infection triggers a change in the transcriptional start site of the zdhhc20 gene, resulting in an extended version of the ZDHHC20 enzyme that enhances the acylating activity of the Spike protein, leading to increased fusion between the virus and host cells. Additionally, the study also revealed that SARS-CoV-2 hijacks an existing cell damage response pathway to optimize its fusion glycoprotein.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Serena Vittorio, Thomas Seidel, Arthur Garon, Rosaria Gitto, Thierry Langer, Laura De Luca
Summary: Protein-protein interactions play a crucial role in physiological processes, and inhibiting them is a promising strategy for designing new anti-tumoral agents. Computational approaches have been successfully used to study these interactions and provide insights for designing small molecules that modulate PPIs. Despite challenges, progress has been made in identifying PPI modulators, some of which have even reached clinical use.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cardiac & Cardiovascular Systems
Madeleine R. Miles, John Seo, Min Jiang, Zachary T. Wilson, Janay Little, Jon Hao, Joshua Andrade, Beatrix Ueberheide, Gea-Ny Tseng
Summary: High-throughput experiments suggest that around 20% of human proteins may undergo S-palmitoylation, with proteins in the cardiac palmitoylome mainly involved in cell-cell junctions and mitochondrial enzyme organization. The cardiac palmitoylome is uniquely enriched in proteins related to the organization of t-tubules, costameres, and intercalated discs.
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2021)
Article
Multidisciplinary Sciences
Vikas Tiwari, Shruthi Viswanath
Summary: This study models the structure of IFITM3 and explores its ligand binding sites. The results suggest potential therapeutic ligands that can alter IFITM3 activity.
SCIENTIFIC REPORTS
(2022)
Article
Automation & Control Systems
Yanwen Li, Feng Pu, Yu Feng, Jinchao Ji, Hongguang Sun, Han Wang
Summary: The paper introduces a computational method named MRMD-Palm for identifying palmitoylated proteins. By collecting palmitoylated and non-palmitoylated proteins to construct a dataset, extracting features, and utilizing the random forest algorithm for prediction, the method achieves high performance.
CHEMOMETRICS AND INTELLIGENT LABORATORY SYSTEMS
(2021)
Article
Biochemistry & Molecular Biology
Anila Hoda, Mirela Lika (Cekani), Valbona Kolaneci
Summary: This study utilized bioinformatics tools and in silico methods to analyze deleterious nsSNPs of the HGF gene. Five nsSNPs were found to have the most significant impact on the structure and function of the HGF protein. Analysis of gene-gene and protein-protein interactions revealed the importance of HGF in multiple pathways and co-expressions.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Biochemistry & Molecular Biology
Denilson Ferreira de Oliveira
Summary: This study aimed to discover binding sites in the SARS-CoV-2 spike protein and select substances capable of efficiently binding to these sites for the development of new products to manage COVID-19 infections. Through docking and pharmacophoric search, five binding sites were identified, and new ligands were designed. Seven substances with good affinities, high druggability, and low acute toxicity to mice were selected as potential candidates for future development.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Multidisciplinary Sciences
Zhenxing Zhang, Xin Li, Fan Yang, Chao Chen, Ping Liu, Yi Ren, Pengkai Sun, Zixiong Wang, Yongping You, Yi-Xin Zeng, Xinjian Li
Summary: This study demonstrates that DHHC9-mediated GLUT1 palmitoylation at Cys207 is essential for plasma membrane localization of GLUT1 and for tumor growth in glioblastoma cells. The findings suggest a potential therapeutic target for targeting GLUT1 in cancer treatment.
NATURE COMMUNICATIONS
(2021)
Article
Microbiology
Dina A. Abdulrahman, Xiaorong Meng, Michael Veit
Summary: Recent pandemics caused by zoonotic coronaviruses and influenza A viruses have shown that viral glycoproteins and ion channels are S-acylated. DHHC family members play a crucial role in palmitoylation, with a common set of DHHCs acylating SARS-CoV-2 and Flu A proteins in human cells. This highlights the potential of DHHCs as targets for broad-spectrum antiviral drugs.
Article
Biochemical Research Methods
Wouter W. Kallemeijn, Thomas Lanyon-Hogg, Nattawadee Panyain, Andrea Goya Grocin, Paulina Ciepla, Julia Morales-Sanfrutos, Edward W. Tate
Summary: Protein lipidation is a widespread post-translational modification in nature that regulates protein function, structure, and subcellular localization. Lipid transferases and their substrate proteins are of interest as drug targets due to their dysregulation in disease. The hydrophobic and dynamic nature of lipid modifications poses challenges for detection, but chemical proteomics offers a powerful approach to identify and quantify them.
Article
Orthopedics
Linghui Ma, Liwei Zhang, Zirui Liao, Chunmei Xiu, Xi Luo, Na Luo, Lei Zhang, Guangxu He, Jianquan Chen
Summary: This study found that protein S-palmitoylation plays a key role in osteoclast differentiation, and inhibiting palmitoylation can suppress osteoclast formation and activity, providing a potential therapeutic target for treating osteoporosis and other osteoclast-related diseases.
JOURNAL OF ORTHOPAEDIC TRANSLATION
(2023)
Article
Cell Biology
Saara-Anne Azizi, Tian Qiu, Noah E. Brookes, Bryan C. Dickinson
Summary: This study reveals that extracellular signal-regulated kinases (ERK1/2) are regulated by S-acylation, and their levels of S-acylation are modulated by epidermal growth factor (EGF) signaling. ERK1/2 S-acylation is mediated by writerprotein acyl transferases (PATs) and eraseracyl protein thioesterases (APTs). Inhibition of lipid addition or removal alters ERK1/2's activity and transcriptional program triggered by EGF. In a mouse model of metabolic syndrome, ERK1/2 lipidation levels correlate with the expression of ERK1/2 lipidation writer/eraser.
Article
Biochemistry & Molecular Biology
Consuelo Coronel Arrechea, Maria Luz Giolito, Iris Alejandra Garcia, Gaston Soria, Javier Valdez Taubas
Summary: Protein palmitoylation, a common post-translational modification, plays important roles in various cancers, neurodegenerative diseases, and infectious diseases. Lack of specific inhibitors has hampered research progress in this field. A yeast-based high-throughput method has been developed to screen for small molecules that inhibit protein palmitoylation effectively.
Review
Biochemistry & Molecular Biology
Jianbo Liao, Qinyu Wang, Fengxu Wu, Zunnan Huang
Summary: Target identification is a crucial step in drug discovery, and computer-aided methods have emerged as an efficient approach. By identifying disease-related targets, their binding sites, and evaluating the druggability of predicted active sites, computer-aided methods greatly reduce the time and cost associated with experimental target identification. This review provides an overview of computer-based active site identification methods, including binding site identification and druggability assessment, offering guidelines for method selection. The review also includes a list of commonly used databases and tools, examples of individual and combined applications, and a comparison of methods and tools. Challenges and limitations of binding site identification and druggability assessment are discussed, along with recommendations and future perspectives.
Article
Biochemistry & Molecular Biology
Kangjia Du, Chengjie Yang, Zhongkun Zhou, Yunhao Ma, Yanan Tian, Rentao Zhang, Hao Zhang, Xinrong Jiang, Hongmei Zhu, Huanxiang Liu, Peng Chen, Yingqian Liu
Summary: A novel isaindigotone derivative BLG26 was synthesized and showed potential anti-proliferation effects in gastric cancer cells, indicating its potential as a candidate drug for gastric cancer treatment. BLG26 exhibited better activity in inhibiting tumor cell proliferation in AGS cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Medicinal
Yuwei Yang, Zhenxing Wu, Xiaojun Yao, Yu Kang, Tingjun Hou, Chang-Yu Hsieh, Huanxiang Liu
Summary: A conditional generative model combining a semisupervised variational autoencoder and a toxicity predictor was developed in this study to generate molecules with low toxicity, good drug-like properties, and structural diversity. The model efficiently generates low-toxicity molecules while maintaining structural diversity during the generation process.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Materials Science, Multidisciplinary
Ping Zhou, Fang Feng, Yameng Song, Jing Li, Qin Li, Zerong Xu, Jiamin Shi, Liying Qin, Fei He, Hongjiao Li, Yu Han, Rongzhi Zhang, Huanxiang Liu, Feng Lan
Summary: The design of novel peptide sequences and investigation of cell adhesion mechanisms are crucial for hiPSCs culture on peptide displaying surfaces. This study reveals the importance of near-Asp sequences in RGD-containing peptides and presents a novel peptide, Ac-KGGVFTMPRGDTYRAY, with excellent ability to sustain hiPSCs cultures. Structural modeling and molecular docking confirm the strong affinity between the peptide and ocV133 integrin protein, contributing to its superior performance. These findings shed light on the mechanisms underlying RGD-containing peptides' support of adhesion and offer a better peptide option for hiPSCs culture.
MATERIALS & DESIGN
(2022)
Article
Chemistry, Physical
Huayi Liu, Yi Zhou, Yingjie Song, Qianqian Zhang, Yeyi Kan, Xinyue Tang, Qingjie Xiao, Qianyin Xiang, Huanxiang Liu, Yunzi Luo, Rui Bao
Summary: CRISPR-Cas9 from Streptococcus pyogenes is a powerful biotechnological tool for DNA sequence modification. Understanding the dynamic mechanism of the REC lobe is crucial for designing and engineering better Cas9 enzymes. The structure analysis of the xCas9 P411T variant and molecular dynamics simulations revealed the central role of REC1 in the activation and target site binding process of Cas9.
Article
Biochemical Research Methods
Yanan Tian, Xiaorui Wang, Xiaojun Yao, Huanxiang Liu, Ying Yang
Summary: This paper proposes a novel graph neural network, IFGN, which gradually identifies the key atoms/groups in the molecule related to predicted properties by a multistep focus mechanism. It also generates multistep interpretations to provide a deeper understanding of the model's predictive behaviors.
BRIEFINGS IN BIOINFORMATICS
(2023)
Review
Biochemical Research Methods
Yuan-Qin Huang, Ping Sun, Yi Chen, Huan-Xiang Liu, Ge-Fei Hao, Bao-An Song
Summary: Drug resistance is a major issue impacting human health and agriculture. Developing approaches to address target mutation-induced drug resistance is crucial in biological research. Bioinformatics tools have been developed over the past decade to explore this type of drug resistance, offering a cost-effective and efficient means of analysis. However, these tools are underutilized and their strengths and limitations have not been thoroughly evaluated. This study systematically surveyed 59 freely available bioinformatics tools and analyzed their functionality, data volume, source, operating principle, and performance. The study also discussed the strengths, limitations, and application examples of these tools, providing a valuable toolbox for researchers in biomedical, pesticide, bioinformatics, and pharmaceutical engineering fields, as well as a platform for non-specialists to understand drug resistance prediction.
BRIEFINGS IN BIOINFORMATICS
(2023)
Article
Biochemical Research Methods
Shukai Gu, Chao Shen, Jiahui Yu, Hong Zhao, Huanxiang Liu, Liwei Liu, Rong Sheng, Lei Xu, Zhe Wang, Tingjun Hou, Yu Kang
Summary: This study evaluated the impact of structural dynamic information on binding affinity prediction and found that the optimized molecular dynamics protocol improved the predictive performance for the TAF1-BD2 target with high structural flexibility, but not for the less flexible JAK1 and DDR1 targets.
BRIEFINGS IN BIOINFORMATICS
(2023)
Article
Biochemistry & Molecular Biology
Fengling Wang, Wenling Ye, Yongxing He, Haiyang Zhong, Yongchang Zhu, Jianting Han, Xiaoqing Gong, Yanan Tian, Yuwei Wang, Shuang Wang, Shaoping Ji, Huanxiang Liu, Xiaojun Yao
Summary: Targeting the PD-1/PD-L1 immunologic checkpoint has provided a breakthrough in cancer therapy. A small molecule inhibitor called CBPA was identified as an effective PD-L1 inhibitor with blocking activity and T-cell reinvigoration capacity. CBPA also showed significant antitumor efficacy in mouse tumor models without observable organ toxicity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Syed Jawad Ali Shah, Qianqian Zhang, Jingjing Guo, Hongli Liu, Huanxiang Liu, Jordi Villa-Freixa
Summary: The microtubule-associated protein tau plays a critical role in the development and protection of the nervous system. Dysfunction and accumulation of tau in the brain can lead to various neurodegenerative diseases. This study reveals the detailed mechanism of acetylation-driven tau aggregation.
ACS CHEMICAL NEUROSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Shuoyan Tan, Jun Wang, Peng Gao, Guotong Xie, Qianqian Zhang, Huanxiang Liu, Xiaojun Yao
Summary: Understanding the selectivity mechanisms of inhibitors for highly similar proteins is crucial in new drug discovery. Developing highly selective targeting of leucine-rich repeat kinase 2 (LRRK2) kinases for Parkinson's disease is challenging due to the similarity of the kinase ATP binding pocket. In this study, computational methods and comprehensive analyses were conducted to investigate the selectivity mechanisms of two representative LRRK2 inhibitors (DNL201 and GNE7915). The results suggest that structural and kinetic differences between the proteins may play a key role in determining the activity of selective small-molecule inhibitors. The proposed selectivity mechanisms could aid in the rational design of novel LRRK2 kinase inhibitors for Parkinson's disease.
ACS CHEMICAL NEUROSCIENCE
(2023)
Article
Biochemical Research Methods
Yang Yue, Shu Li, Lingling Wang, Huanxiang Liu, Henry H. Y. Tong, Shan He
Summary: In this study, a novel framework called MpbPPI is proposed for accurate prediction of amino acid mutations on protein-protein interactions. Pre-training on a strictly screened dataset enables MpbPPI to generate high-quality representations and support flexible application on different mutant-type protein-protein complexes.
BRIEFINGS IN BIOINFORMATICS
(2023)
Article
Biochemistry & Molecular Biology
Yunhao Ma, Hongmei Zhu, Xinrong Jiang, Zhongkun Zhou, Yong Zhou, Yanan Tian, Hao Zhang, Mengze Sun, Lixue Tu, Juan Lu, Yuqing Niu, Huanxiang Liu, Yingqian Liu, Peng Chen
Summary: This study evaluated the cytotoxicity of 8-methoxy-2,5-dimethyl-5H-indolo[2,3-b]quinoline (MMNC) in colorectal cancer cells and found that MMNC exerted cytotoxicity by inhibiting the expression of PI3K/AKT/mTOR signaling pathway-related proteins, inhibiting cell proliferation, blocking the cell cycle, and inducing apoptosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Medicinal
Zhe Wang, Haiyang Zhong, Jintu Zhang, Peichen Pan, Dong Wang, Huanxiang Liu, Xiaojun Yao, Tingjun Hou, Yu Kang
Summary: This study systematically evaluates the performance of traditional methods and AI models in small-molecule conformer generation. The results show that traditional methods outperform AI models in reproducing bioactive conformations, while an AI model has an advantage in generating low-energy conformations.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Chemistry, Medicinal
Jieyu Jin, Dong Wang, Guqin Shi, Jingxiao Bao, Jike Wang, Haotian Zhang, Peichen Pan, Dan Li, Xiaojun Yao, Huanxiang Liu, Tingjun Hou, Yu Kang
Summary: Recently, deep generative models, such as FFLOM, have shown promise in fragment-based drug design by generating molecules with desired properties. FFLOM achieves state-of-the-art performance in terms of validity, uniqueness, novelty, and recovery of generated molecules. It also demonstrates excellent potential in practical scenarios including fragment linking, PROTAC design, R-group growing, and R-group optimization, generating molecules with novel fragments and higher binding affinity.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Chemistry, Multidisciplinary
Jingjing Guo, Yiqiong Bao, Mengrong Li, Shu Li, Lili Xi, Pengyang Xin, Lei Wu, Huanxiang Liu, Yuguang Mu
Summary: Biological membranes are complex structures vital for life. Experimental investigation of biomembranes is challenging, but computational approaches such as molecular dynamics (MD) simulations have provided insights into their atomic details and cellular functions. This review highlights the latest advancements in computational methods, from force fields to MD simulations and trajectory analysis. It also discusses current research topics, challenges, and future directions for applying computational technologies in biomembrane systems.
WILEY INTERDISCIPLINARY REVIEWS-COMPUTATIONAL MOLECULAR SCIENCE
(2023)