Article
Chemistry, Medicinal
Wenqing Zhang, Kan Li, Tianqi Wang, Ming Wu, Linli Li
Summary: This study identified seven JMJD7 inhibitors using consensus docking/scoring strategy and bioactivity evaluation, with Cpd-3 being the most potent compound showing efficient binding to JMJD7 in vitro and displaying good inhibitory activity against cancer cell lines expressing high levels of JMJD7. Overall, this research provided a solid foundation for drug discovery targeting JMJD7.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Chemistry, Medicinal
Chao Shen, Xujun Zhang, Yafeng Deng, Junbo Gao, Dong Wang, Lei Xu, Peichen Pan, Tingjun Hou, Yu Kang
Summary: In recent years, machine learning approaches have made significant progress in the development of protein-ligand scoring functions. However, the robustness and wide applicability of scoring functions still pose a challenge in increasing the success rate of docking-based virtual screening. In this study, a new scoring function called RTMScore is proposed, which incorporates a tailored residue-based graph representation strategy and multiple graph transformer layers for learning protein and ligand representations. The results demonstrate that RTMScore outperforms state-of-the-art methods in terms of both docking and screening powers, and it shows robustness in cross-docking poses and improved performance in larger-scale virtual screening as a rescoring tool.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
Huizhen Ge, Lizeng Peng, Zhou Sun, Huanxiang Liu, Yulin Shen, Xiaojun Yao
Summary: In this study, novel HPK1 inhibitors were identified using virtual screening and kinase inhibition assays. Molecular dynamics simulations were performed to analyze the interaction between the identified compounds and HPK1 kinase domain. The most potent compound showed potential for further development as an HPK1 inhibitor for immunotherapy.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Yatong Li, Yuxin Zhang, Xia Wu, Yanbin Gao, Junfang Guo, Yulang Tian, Ziyue Lin, Xing Wang
Summary: Chinese herbal medicines are commonly used to treat inflammatory diseases, and this study identified natural 15-LOX inhibitors in CHM using virtual screening combined with biological assays. The inhibitors licochalcone B and eriodictyol were confirmed to suppress 15-LOX enzyme activity and reduce TNF-alpha release in RAW264.7 cells, providing a basis for further research and development of 15-LOX inhibitors.
BIOORGANIC CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Xue-ping Hu, Liu Yang, Xin Chai, Yi-xuan Lei, Md Shah Alam, Lu Liu, Chao Shen, De-jun Jiang, Zhe Wang, Zhi-yong Liu, Lei Xu, Kang-lin Wan, Tian-yu Zhang, Yue-lan Yin, Dan Li, Dong-sheng Cao, Ting-jun Hou
Summary: This study utilized an integrated molecular modeling strategy to identify two lead compounds that could inhibit DprE1 and showed inhibitory activity against Mycobacterium tuberculosis in vitro, with low cytotoxicity against mouse embryo fibroblast NIH-3T3 cells. This research provides an effective strategy for discovering novel anti-TB lead compounds.
ACTA PHARMACOLOGICA SINICA
(2022)
Article
Biochemistry & Molecular Biology
Naomi Scarano, Elena Abbotto, Francesca Musumeci, Annalisa Salis, Chiara Brullo, Paola Fossa, Silvia Schenone, Santina Bruzzone, Elena Cichero
Summary: This article focuses on the selective inhibitors of SIRT2 enzyme. By using SBVS method, a potential molecular scaffold for designing new SIRT2 inhibitors was identified. Experimental results showed that this molecular scaffold exhibited strong SIRT2 inhibitory activity, validating the effectiveness of the research strategy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Hui Zhu, Yulin Zhang, Wei Li, Niu Huang
Summary: Structure-based virtual screening, also known as molecular docking, has gained increasing application in the early stage of drug discovery for discovering small-molecule ligands based on protein structures. This review comprehensively surveys the prospective applications of molecular docking with solid experimental validations. The analysis includes the novelty of targets and docking hits, practical protocols of docking screening, and the subsequent experimental validations. The majority of virtual screenings were performed on widely studied targets, with only a small portion focused on less-explored new targets. GLIDE is the most popular docking software, while the DOCK 3 series excels in large-scale virtual screening. The identified hits are promising in structural novelty, with a quarter of them exhibiting better potency than 1 μM. However, most studies only conducted in vitro bioassays for validation, potentially limiting the further characterization and development of the active compounds.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Multidisciplinary
Chao Shen, Xueping Hu, Junbo Gao, Xujun Zhang, Haiyang Zhong, Zhe Wang, Lei Xu, Yu Kang, Dongsheng Cao, Tingjun Hou
Summary: Structure-based drug design relies on detailed knowledge of protein-ligand binding complexes, but accurate prediction of ligand-binding poses remains challenging. This study developed XGBoost-trained classifiers using a cross-docking dataset from the PDBbind database to discriminate binding poses, showing that specific features such as ECIF and Vina energy terms significantly impact performance, and inclusion of Vina energy terms in training can enhance model generalization.
JOURNAL OF CHEMINFORMATICS
(2021)
Article
Biochemistry & Molecular Biology
Ruijuan Liu, Xuewei Liu
Summary: Through structure-based virtual screening, this study identified 47 potential inhibitors of HK-II, with nine compounds showing high cytotoxicity to cancer cells. Two compounds demonstrated significant inhibitory effects on the HK-II enzyme, suggesting potential for future tumor therapy.
Article
Biochemistry & Molecular Biology
Vibhu Jha, Salvatore Galati, Valerio Volpi, Lidia Ciccone, Filippo Minutolo, Flavio Rizzolio, Carlotta Granchi, Giulio Poli, Tiziano Tuccinardi
Summary: ACLY is an important enzyme involved in fatty acid synthesis and could be a promising target for anticancer drug design. Through virtual screening, compound VS1 with potential inhibitory activity was identified, showing a 2.5 times higher potency than the reference inhibitor 2-hydroxycitrate.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2021)
Article
Biochemistry & Molecular Biology
Akshita Gupta, Viswanathan Vijayan, Pradeep Pant, Punit Kaur, Tej P. Singh, Pradeep Sharma, Sujata Sharma
Summary: Acinetobacter baumannii is a dangerous MDR gram-negative pathogen, and this study identified 6 potential drug candidates targeting the unique bacterial PPCS structure through structure-based drug design.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Chemistry, Multidisciplinary
Shan-Kui Liu, Haifang Hao, Yuan Bian, Yong-Xi Ge, Shengyuan Lu, Hong-Xu Xie, Kai-Ming Wang, Hongrui Tao, Chao Yuan, Juan Zhang, Jie Zhang, Cheng-Shi Jiang, Kongkai Zhu
Summary: In this study, 52 candidates of alpha-glycosidase inhibitors were screened from a commercial compound library, with 4 identified compounds showing promising inhibitory activities and noncompetitive binding modes. These compounds exhibited low toxicity in human cells, indicating their potential as novel treatments for type 2 diabetes.
FRONTIERS IN CHEMISTRY
(2021)
Article
Pharmacology & Pharmacy
Chujiao Hu, Zhirui Zeng, Dan Ma, Zhixin Yin, Shanshan Zhao, Tengxiang Chen, Lei Tang, Shi Zuo
Summary: In this study, novel inhibitors of IDH1-R132C were identified using virtual screening and cellular assays. Compound T001-0657 showed the most potent inhibitory effect against cancer cells harboring the IDH1-R132C mutation, while also exhibiting cytotoxicity against wild-type IDH1 cancer cells and normal cells.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Chemistry, Medicinal
Chayanin Hanwarinroj, Nareudon Phusi, Bundit Kamsri, Pharit Kamsri, Auradee Punkvang, Sombat Ketrat, Patchreenart Saparpakorn, Supa Hannongbua, Khomson Suttisintong, Prasat Kittakoop, James Spencer, Adrian J. Mulholland, Pornpan Pungpo
Summary: This study used in silico screening approaches to discover four novel InhA inhibitors with potential activity against Mycobacterium tuberculosis. The binding interactions and binding energy of the candidate compounds were investigated using molecular mechanics calculations. These compounds showed suitable physicochemical, pharmacokinetic, and antibacterial properties, making them promising hit compounds for further experimental studies.
FUTURE MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Congzhou M. Sha, Jian Wang, Nikolay V. Dokholyan
Summary: Virtual screening is a cost- and time-effective alternative to traditional high-throughput screening in the drug discovery process. NeuralDock, a neural network framework, accelerates computational docking and accurately predicts binding energy and affinity of protein-small molecule pairs without prior knowledge of a ligand. It has the potential to be useful in brute-force virtual screening and drug model training.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Zhaofeng Ye, Matthew P. Baumgartner, Bentley M. Wingert, Carlos J. Camacho
JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN
(2016)
Article
Biochemistry & Molecular Biology
Bentley M. Wingert, Rick Oerlemans, Carlos J. Camacho
JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN
(2018)
Review
Biochemistry & Molecular Biology
Bentley M. Wingert, Carlos J. Camacho
CURRENT OPINION IN CHEMICAL BIOLOGY
(2018)
Article
Biochemistry & Molecular Biology
Bentley M. Wingert, Eric E. Parrott, Scott W. Nelson
Article
Biochemistry & Molecular Biology
Bentley Wingert, James Krieger, Hongchun Li, Ivet Bahar
Summary: Many proteins select from a small repertoire of 3-dimensional folds that have been retained over evolutional timescales and recruited for different functions. Recent studies have shown the evolutionary constraints on protein dynamics to achieve function, highlighting the importance of balancing conformational flexibility and stability. The design principles illustrated for the family of PDZ domains demonstrate how dynamic and structural balance is key to achieving efficient function.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2021)