Article
Multidisciplinary Sciences
Biswaranjan Mohanty, Julien Orts, Geqing Wang, Stefan Nebl, Wesam S. Alwan, Bradley C. Doak, Martin L. Williams, Begona Heras, Mehdi Mobli, Martin J. Scanlon
Summary: The structures of protein-ligand complexes are crucial for drug design, and are mainly determined using X-ray crystallography. However, when crystallography fails, NMR is often used as an alternative method. Unfortunately, the tools available for rapid and robust structure determination of protein-ligand complexes by NMR are currently limited. In this study, the NMR2 approach is described, which allows the determination of the binding pose of a small molecule in a weak protein-ligand complex by collecting sparse protein methyl-to-ligand NOEs from a selectively labeled protein sample and an unlabeled ligand. This approach extends the utility of NMR2 to larger protein-ligand complexes.
SCIENTIFIC REPORTS
(2022)
Article
Chemistry, Multidisciplinary
Manuel Cordova, Lyndon Emsley
Summary: The determination of the molecular solid structure using NMR crystallography relies on generating a comprehensive set of candidate crystal structures and comparing computed chemical shifts with experimental values. However, exploring the polymorph landscape of molecular solids requires a significant computational power, leading to a bottleneck in candidate crystal generation. This study constructs three-dimensional interaction maps using a crystal structure database with associated chemical shifts to identify structural constraints for accelerating crystal structure prediction protocols, without requiring DFT-level chemical shift computations.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Review
Pharmacology & Pharmacy
Md. Moinul, Samima Khatun, Sk. Abdul Amin, Tarun Jha, Shovanlal Gayen
Summary: This review discusses the application of fragment-based drug design in cancer treatment, as well as the design strategies for different targets, providing insights for finding suitable lead compounds through fragment-based design in high throughput screening.
BIOCHEMICAL PHARMACOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Murtala A. Ejalonibu, Segun A. Ogundare, Ahmed A. Elrashedy, Morufat A. Ejalonibu, Monsurat M. Lawal, Ndumiso N. Mhlongo, Hezekiel M. Kumalo
Summary: Developing new antibiotics targeting resistant Mycobacterium tuberculosis is an appealing strategy to combat the global tuberculosis epidemic, with computational techniques playing a key role in drug design and discovery. Recent advancements in technology have enhanced the chances of drug development, offering hope in the fight against tuberculosis resistance.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Multidisciplinary
Martins Balodis, Manuel Cordova, Albert Hofstetter, Graeme M. Day, Lyndon Emsley
Summary: The determination of the three-dimensional atomic-level structure of powdered solids is an important goal in current chemistry. This study successfully determined the crystal structures of ampicillin, piroxicam, cocaine, and two polymorphs of the drug molecule AZD8329 using machine-learned isotropic chemical shifts generated on-the-fly to guide a Monte Carlo-based structure determination process.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Review
Biochemistry & Molecular Biology
Palina Pliushcheuskaya, Georg Kuenze
Summary: Ion channels are involved in various essential biological processes and targeting them with drugs has potential therapeutic applications. However, the development of selective drugs for ion channels lags behind due to limited understanding. Computational approaches, especially structure-based drug design, can accelerate early stages of drug discovery and offer new opportunities for research. This review emphasizes the importance of integrating structural data, modeling, and chemoinformatics to identify and characterize new molecules targeting ion channels.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Luke F. Duncan, Geqing Wang, Olga Ilyichova, Rabeb Dhouib, Makrina Totsika, Martin J. Scanlon, Begona Heras, Belinda M. Abbott
Summary: This study elucidates the binding mode of benzofuran derivatives to the active site of bacterial DsbA and their inhibitory effect on its activity, providing a basis for the development of novel anti-virulence compounds.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Seho Lee, Chaok Seok, Hahnbeom Park
Summary: In this study, we evaluate the usefulness of cryo-EM protein structures for in silico drug design by analyzing ligand docking accuracy. Our results show that medium resolution cryo-EM structures have lower docking success rates compared to high-resolution crystal structures. We identify the heterogeneity in protein conformations as the main factor causing docking difficulties in cryo-EM structures. We suggest the need for more robust method developments to fully utilize cryo-EM structures in drug design.
JOURNAL OF COMPUTATIONAL CHEMISTRY
(2023)
Review
Biochemistry & Molecular Biology
Emilio Mateev, Maya Georgieva, Alexandrina Mateeva, Alexander Zlatkov, Shaban Ahmad, Khalid Raza, Vasco Azevedo, Debmalya Barh
Summary: With the increase in neurodegenerative diseases, monoamine oxidase type B (MAO-B) inhibitors are emerging as promising structures for treatment. Structure-based virtual screening (SBVS), specifically using molecular docking, is a useful tool for drug discovery and development. This study provides insight into the role of MAOs in treating neurodegenerative diseases, discusses the advantages and disadvantages of docking simulations and software, and explores the active sites of MAO-A and MAO-B. New chemical classes of MAO-B inhibitors and their essential fragments are also discussed, providing potential directions for further research.
Review
Pharmacology & Pharmacy
Juan Di Filippo, Claudio N. Cavasotto
Summary: The implementation of AI methodologies in drug discovery is increasing, particularly in structure-based virtual screening. AI methods provide alternative frameworks for ligand identification and de novo ligand design. Future trends include more structure-based generative models and standard guidelines for validating generated structures.
EXPERT OPINION ON DRUG DISCOVERY
(2022)
Article
Chemistry, Medicinal
Hugo Guterres, Sang-Jun Park, Yiwei Cao, Wonpil Im
Summary: The study introduces CHARMM-GUI Ligand Designer, a tool for designing virtual ligands that match the shape and chemical features of a given protein binding site. The tool is shown to produce similar ligands to known active ligands in crystal structures and generate stable protein-ligand complex structures with 3D visualization.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2021)
Review
Biochemistry & Molecular Biology
Balazs Zoltan Zsido, Bayartsetseg Bayarsaikhan, Rita Borzsei, Viktor Szel, Violetta Mohos, Csaba Hetenyi
Summary: Water plays a crucial role in various natural processes, and therefore molecular engineering must consider the structural and energetic effects of hydration. This review focuses on target-ligand interactions in drug design, particularly in biomolecules, but the methods and applications can be adapted to other areas of molecular complex engineering, including solid hydrates. The review discusses the determination of water structures, encompassing experimental approaches, theoretical calculations, and conceptual classifications. It also highlights the use of water models in calculating binding thermodynamics and performing computational ligand docking. The review concludes that theoretical approaches not only replicate or enhance experimental water structures but also provide essential insights into the contributions of individual water molecules, making them indispensable tools in molecular engineering.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Mandar T. Naik, Nandita Naik, Tony Hu, Szu-Huan Wang, John Marshall
Summary: This study developed a new series of compounds that target specific proteins involved in the brain-derived neurotrophic factor signaling pathway, potentially improving therapeutic interventions for depression and other neurological disorders.
Article
Biology
Swati Krishna, S. Birendra Kumar, T. P. Krishna Murthy, Manikanta Murahari
Summary: The BCL-2 family plays a crucial role in cellular apoptosis, with the overexpression of anti-apoptotic members linked to cell death evasion and cancer metastasis. BH3-mimetic drugs are being explored as BCL-2 inhibitors, with ZINC68728276 and ZINC14166367 identified as potential inhibitors in silico.
COMPUTERS IN BIOLOGY AND MEDICINE
(2021)
Review
Chemistry, Medicinal
Smriti Sharma, Vinayak Bhatia
Summary: Pyrazole and its derivatives are pharmacologically active scaffolds with various potential applications in drug discovery. Computational techniques such as molecular docking and molecular dynamics simulations play a crucial role in designing drugs based on pyrazole moieties. Integration of experimental and computational approaches is essential for maximizing the pharmacological potential of pyrazole derivatives.
MINI-REVIEWS IN MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Bin Guo, Yichen Zhang, Gregory Hicks, Xingrong Huang, Rongfeng Li, Natalie Roy, Zongchao Jia
ACS CHEMICAL BIOLOGY
(2019)
Article
Biochemistry & Molecular Biology
Zhen Lei, Biying Wang, Zhifang Lu, Nan Wang, Hongwei Tan, Jimin Zheng, Zongchao Jia
Article
Biochemistry & Molecular Biology
Zhen Lei, Nan Wang, Hongwei Tan, Jimin Zheng, Zongchao Jia
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Biochemistry & Molecular Biology
Yichen Zhang, Shu Wang, Zongchao Jia
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Correction
Multidisciplinary Sciences
Xiaoying Zhang, Qingya Shen, Zhen Lei, Qianyi Wang, Jimin Zheng, Zongchao Jia
SCIENTIFIC REPORTS
(2020)
Article
Biochemistry & Molecular Biology
Wenping Wu, Qingya Shen, Ruiling Zhang, Zhiyu Qiu, Youjun Wang, Jimin Zheng, Zongchao Jia
Article
Chemistry, Inorganic & Nuclear
Jacob Joel Kirsh Carson, Caitlin Elizabeth Miron, Jingwei Luo, Jean-Louis Mergny, Laura van Staalduinen, Zongchao Jia, Anne Petitjean
Summary: This study explores the isomerization process of square planar platinum(II) complexes composed of two different length bidentate ligands, using various analytical techniques to analyze their potential impact on interactions with biomolecules.
INORGANICA CHIMICA ACTA
(2021)
Article
Microbiology
Nolan Neville, Nathan Roberge, Xiang Ji, Preyesh Stephen, Jiasheng Louis Lu, Zongchao Jia
Summary: The small molecule gallein was discovered as a dual-specificity inhibitor of both PPK1 and PPK2 enzyme families in Pseudomonas aeruginosa, disrupting cellular polyphosphate accumulation and attenuating biofilm formation, motility, and toxin production. This study establishes PPK2 enzymes as valuable drug targets in P. aeruginosa and provides a promising starting point for the development of new antivirulence therapeutics.
Review
Biochemistry & Molecular Biology
Nolan Neville, Nathan Roberge, Zongchao Jia
Summary: Inorganic polyphosphate (polyP) plays a crucial role in various biological functions in bacteria, and polyphosphate kinase (PPK) enzymes are key enzymes involved in polyP synthesis and regulation. This review focuses on the roles and functions of PPK2 enzymes in bacteria and discusses developing drugs that target PPK2 as a novel strategy for combating bacterial infections.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Zhifang Lu, Biying Wang, Zhiyu Qiu, Ruiling Zhang, Jimin Zheng, Zongchao Jia
Summary: Bacterial cryptic prophage genes can significantly influence host physiology by encoding lytic proteins. This study reveals that YdfD from the Qin cryptic prophage interacts with the key enzyme IspG in the MEP pathway, leading to compromised cell membrane and cell wall biosynthesis and eventual cell lysis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Food Science & Technology
Bin Guo, Fang Chou, Libin Huang, Feifan Yin, Jing Fang, Jian-Bo Wang, Zongchao Jia
Summary: Quercetin, the most abundant polyphenolic flavonoid in vegetal foods and medicinal plants, has multiple beneficial health effects. However, controversies exist regarding its antioxidant and pro-oxidant properties, stability and bioavailability, and its exact roles in vivo. Recent evidence suggests that the oxidation of quercetin to generate diverse chemical compounds is a new linkage to its versatile actions.
CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION
(2022)
Article
Multidisciplinary Sciences
Biying Wang, Hairun Pei, Zhifang Lu, Yingying Xu, Shengnan Han, Zongchao Jia, Jimin Zheng
Summary: YihE interacts with Rho to form a complex with a stoichiometric ratio of 6:1 (Rho:YihE). YihE serves as a Rho antagonist by competing with RNA for Rho binding, thereby regulating transcription termination to help bacteria cope with stress.
Review
Biochemistry & Molecular Biology
Kody A. Klupt, Zongchao Jia
Summary: The alpha-kinase eEF2K phosphorylates eEF2 at its threonine 56 residue to inhibit protein translation. Investigation into eEF2K targeting involves structure-based drug design using computational techniques. eEF2K plays diverse roles in diseases like cancer and neurological disorders, and inhibiting it is considered a potential treatment option. This review discusses the use of homology modeling with crystal structures of related alpha-kinases to improve inhibitor design, as well as the history of eEF2K-related drug discovery and future prospects with the availability of eEF2K crystal structure.