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Advancements in Structural Biology – How to See Molecules of Life? 结构生物学的进步--如何观察生命分子?
Postepy biochemii Pub Date : 2024-07-01 DOI: 10.18388/pb.2021_533
Wojciech Witek, Wiktoria Ragin, Ha Linh Tran, Ewa Połomska, Mikołaj Podlewski, Aleksandra Pawłowicz, Aleksandra Cioch-Biniaś, Amadeusz Woś, Witold Andrałojć, Marta Szachniuk, Miłosz Ruszkowski
{"title":"Advancements in Structural Biology – How to See Molecules of Life?","authors":"Wojciech Witek, Wiktoria Ragin, Ha Linh Tran, Ewa Połomska, Mikołaj Podlewski, Aleksandra Pawłowicz, Aleksandra Cioch-Biniaś, Amadeusz Woś, Witold Andrałojć, Marta Szachniuk, Miłosz Ruszkowski","doi":"10.18388/pb.2021_533","DOIUrl":"https://doi.org/10.18388/pb.2021_533","url":null,"abstract":"<p><p>Structural biology is focused on understanding the architecture of biomolecules, such as proteins and nucleic acids. Deciphering the structure helps to understand their function in the cell at a very precise – molecular level. This makes it possible to not only determine the basis of diseases but also to propose therapeutic strategies and tools. Such a strong motivation for the development of structural biology has led to the development of a number of methods, which enable determination of the structures of the molecules of life. The continuous progress has been enabled by the integration of biology, chemistry, physics, and computer science, making structural biology extremely interdisciplinary. In its 35-year history, the Institute of Bioorganic Chemistry of the Polish Academy of Sciences in Poznan has become one of the key Polish institutions conducting research in the field of structural biology. On one hand, the research has brought international recognition, and on the other hand, it has forced the implementation and development of cutting-edge methods. This review discusses the methods used in structural biology at the Institute.</p>","PeriodicalId":20335,"journal":{"name":"Postepy biochemii","volume":"70 2","pages":"128-138"},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141860682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Chemical simulations of quantum systems using quantum computers - review of algorithms and their experimental verification 利用量子计算机对量子系统进行化学模拟 - 算法及其实验验证综述
Postepy biochemii Pub Date : 2024-07-01 DOI: 10.18388/pb.2021_536
Konrad Wojciechowski, Krzysztof Kurowski, Cezary Mazurek
{"title":"Chemical simulations of quantum systems using quantum computers - review of algorithms and their experimental verification","authors":"Konrad Wojciechowski, Krzysztof Kurowski, Cezary Mazurek","doi":"10.18388/pb.2021_536","DOIUrl":"https://doi.org/10.18388/pb.2021_536","url":null,"abstract":"<p><p>Computer simulations using ever-increasing computing power and machine learning techniques allow advanced molecular modelling, molecular dynamics simulations and studies of intermolecular interactions. However, due to the complexity of biological systems and chemical processes at the molecular level, their accurate representation using classical computer models and techniques has faced a number of significant limitations for many years. A new and promising direction for the development of computational science and its potential applications in biochemistry is quantum computing and its integration with classical high-performance supercomputing systems. This article responds to the growing interest in the use of available quantum computers in exemplary applications. In this paper, we aim to provide an overview of the basic notions involved in the development of quantum algorithms and simulations related to issues at the interface of quantum chemistry and biochemistry. In addition, the article introduces the basic principles of performing simulations using the state-of-the-art quantum computers in the era of Noisy Intermediate-Scale Quantum (NISQ). Experimental results of the classical-quantum algorithm Variational Quantum Eigensolver (VQE) for example molecules H2 and CH+ are also presented. Despite the many shortcomings of currently available quantum computers, the analysed VQE algorithm proved to be effective in approximating the ground state of molecules using a minimal functional basis.</p>","PeriodicalId":20335,"journal":{"name":"Postepy biochemii","volume":"70 2","pages":"257-265"},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141860685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
From Sanger to genome sequencing - an overview of DNA sequencing technologies 从桑格到基因组测序--DNA 测序技术概览
Postepy biochemii Pub Date : 2024-07-01 DOI: 10.18388/pb.2021_534
Małgorzata Marcinkowska-Swojak, Magdalena Rakoczy, Jan Podkowiński, Jurand Handschuh, Paweł Wojciechowski, Luiza Handschuh
{"title":"From Sanger to genome sequencing - an overview of DNA sequencing technologies","authors":"Małgorzata Marcinkowska-Swojak, Magdalena Rakoczy, Jan Podkowiński, Jurand Handschuh, Paweł Wojciechowski, Luiza Handschuh","doi":"10.18388/pb.2021_534","DOIUrl":"https://doi.org/10.18388/pb.2021_534","url":null,"abstract":"<p><p>There is no technique that would make a greater contribution to the development of genetics, molecular biology and medicine than DNA sequencing. For many years, the method based on enzymatic DNA synthesis developed by Frederic Sanger was the gold standard in this area. At the end of the 20th century, there was a dynamic development of next-generation sequencing (NGS) technologies, which ended the era of single gene analysis and initiated the era of genome sequencing. Despite fierce competition, one NGS technology has practically completely dominated the global market. In the article, we present our own review of DNA sequencing methods, starting from the Sanger method to high-throughput second- and third-generation sequencing technologies, with particular emphasis on those that have achieved commercial success. We present their short history, principles of operation, technical possibilities, applications and limitations. In the summary, we reveal how much human genome sequencing costs at the current stage of the genomic revolution and outline the prospects for further development of genomics.</p>","PeriodicalId":20335,"journal":{"name":"Postepy biochemii","volume":"70 2","pages":"173-189"},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141860686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Advances in the development of synthetic biology tools for the bioproduction of natural product analogues 开发用于生物生产天然产品类似物的合成生物学工具的进展情况
Postepy biochemii Pub Date : 2024-07-01 DOI: 10.18388/pb.2021_531
Piotr Michałowski, Aleksandra Bigos, Dorota Jakubczyk
{"title":"Advances in the development of synthetic biology tools for the bioproduction of natural product analogues","authors":"Piotr Michałowski, Aleksandra Bigos, Dorota Jakubczyk","doi":"10.18388/pb.2021_531","DOIUrl":"https://doi.org/10.18388/pb.2021_531","url":null,"abstract":"<p><p>Chemical compounds of natural origin, the so-called natural products and their derivatives, constitute the basis of medicines. They are widely used, among others, in the agricultural, veterinary, food and cosmetics industries. The article presents the division of natural products, with particular emphasis on bioactive secondary metabolites, and progress in the development of synthetic biology tools for their bioproduction.</p>","PeriodicalId":20335,"journal":{"name":"Postepy biochemii","volume":"70 2","pages":"246-256"},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141860683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The transcriptome of acute dehydration in myeloid leukemic cells. 骨髓性白血病细胞急性脱水的转录组
Postepy biochemii Pub Date : 2024-05-23 DOI: 10.18388/pb.2021_507
David B Mark Welch, Travis J Gould, Ada L Olins, Donald E Olins
{"title":"The transcriptome of acute dehydration in myeloid leukemic cells.","authors":"David B Mark Welch, Travis J Gould, Ada L Olins, Donald E Olins","doi":"10.18388/pb.2021_507","DOIUrl":"https://doi.org/10.18388/pb.2021_507","url":null,"abstract":"<p><p>Human myeloid leukemia cells (HL-60/S4) exposed to hyperosmotic stress with sucrose undergo dehydration and cell shrinkage. Interphase chromatin and mitotic chromosomes congeal, exhibiting altered phase separation (demixing) of chromatin proteins. To investigate changes in the transcriptome, we exposed HL-60/S4 cells to hyperosmotic sucrose stress (~600 milliOsmolar) for 30 and 60 minutes. We employed RNA-Seq of polyA mRNA to identify genes with increased or decreased transcript levels relative to untreated control cells (i.e., differential gene expression). These genes were examined for over-representation of Gene Ontology (GO) terms.  In stressed cells, multiple GO terms associated with transcription, translation, mitochondrial function and proteosome activity, as well as \"replication-dependent histones\", were over-represented among genes with increased transcript levels; whereas, genes with decreased transcript levels were over-represented with transcription repressors. The transcriptome profiles of hyperosmotically-stressed cells suggest acquisition of cellular rebuilding, a futile homeostatic response, as these cells are ultimately doomed to a dehydrated death.</p>","PeriodicalId":20335,"journal":{"name":"Postepy biochemii","volume":"70 1","pages":"41-51"},"PeriodicalIF":0.0,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141627422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
From single DNA adducts measurement to DNA adductomics in molecular epidemiology of cancer. 从单一 DNA 加合物测量到癌症分子流行病学中的 DNA 加合物组学。
Postepy biochemii Pub Date : 2024-05-23 DOI: 10.18388/pb.2021_509
Wanda Baer-Dubowska, Hanna Szaefer
{"title":"From single DNA adducts measurement to DNA adductomics in molecular epidemiology of cancer.","authors":"Wanda Baer-Dubowska, Hanna Szaefer","doi":"10.18388/pb.2021_509","DOIUrl":"https://doi.org/10.18388/pb.2021_509","url":null,"abstract":"<p><p>Environmental carcinogens exert their carcinogenic effects by forming DNA adducts. This type of DNA damage can also be formed endogenously as a result of, e.g., oxidative damage. Unrepaired  DNA adducts may induce mutations in critical genes, leading to the initiation of chemical carcinogenesis. Therefore,  detection, identification, and quantification of DNA adducts is essential for cancer risk assessment. Over the last 50 years, the major DNA adducts formed by different classes of environmental carcinogens were characterized. With the development of techniques such as 32P-postlabeling, their measurement was implemented into molecular epidemiology. Advances in liquid chromatography-tandem mass spectrometry (LC-MS ) made the measurement of adducts more precise  and allowed to gain knowledge about their identity and structures. Therefore,  opened the way to  DNA adductomics, the  \"omics\" approach investigating DNA adducts comprehensively, similarly to proteomics. This review presents the historical perspective of DNA adducts research and the emerging field of adductomics.</p>","PeriodicalId":20335,"journal":{"name":"Postepy biochemii","volume":"70 1","pages":"52-56"},"PeriodicalIF":0.0,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141627421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Assessment of metabolomics in patients with multiple sclerosis as an indicator of disease development, including relapsing-remitting, primary progressive and secondary progressive stage 评估多发性硬化症患者的代谢组学作为疾病发展的指标,包括复发缓解期、原发性进展期和继发性进展期
Postepy biochemii Pub Date : 2023-09-03 Print Date: 2023-09-30 DOI: 10.18388/pb.2021_492
Mikołaj Górka, Magdalena Dębiec, Natalia Białoń, Dominika Bieczek, Krzysztof Suszyński, Dariusz Górka
{"title":"Assessment of metabolomics in patients with multiple sclerosis as an indicator of disease development, including relapsing-remitting, primary progressive and secondary progressive stage","authors":"Mikołaj Górka, Magdalena Dębiec, Natalia Białoń, Dominika Bieczek, Krzysztof Suszyński, Dariusz Górka","doi":"10.18388/pb.2021_492","DOIUrl":"https://doi.org/10.18388/pb.2021_492","url":null,"abstract":"<p><p>Metabolomics is a scientific field whose topics include qualitative and quantitative analysis of metabolites, defined as the total set of low-molecular-weight chemical compounds not exceeding 1500 Da. Along with genomics, transcriptomics, and proteomics, it is categorized as a field of science, currently using state-of-the-art diagnostic tools that, in the face of modern medicine, allow a holistic approach to the patient. The presence of metabolites in the analyzed biological material, in contrast to the information contained directly in the genetic material, reflects the current physiological state of the cell, and represents an integral relationship between genotype and phenotype, which can directly contribute in the future to the knowledge of the molecular basis in specific disease entities. An additional aspect that is in favor of metabolic analysis is their decidedly smaller number compared to at least genes, transcriptomes, and proteins. Despite the development of many \"omics\" technologies, there is a lack of integrative and linking studies to see the full picture of cellular pathways in the future. Such linkage would improve our insight into human pathologies, leading to a revolution in preclinical and clinical research in disease diagnosis, prognosis, drug response and drug development.</p>","PeriodicalId":20335,"journal":{"name":"Postepy biochemii","volume":"69 3","pages":"188-198"},"PeriodicalIF":0.0,"publicationDate":"2023-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138462158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
From a mutation to a drug 从突变到药物
Postepy biochemii Pub Date : 2023-09-03 Print Date: 2023-09-30 DOI: 10.18388/pb.2021_498
Jan Wnuk, Tomasz Wilanowski
{"title":"From a mutation to a drug","authors":"Jan Wnuk, Tomasz Wilanowski","doi":"10.18388/pb.2021_498","DOIUrl":"10.18388/pb.2021_498","url":null,"abstract":"<p><p>Malignant melanoma is a dangerous skin cancer, accounting for the majority of skin cancer-related deaths. Many patients with this cancer have the V600E mutation in the BRAF gene. This mutation causes constitutive activation of the MAPK/ERK signaling pathway, significantly contributing to the process of carcinogenesis. We discuss the drug design process on the example of a specific BRAF V600E inhibitor, vemurafenib. We begin with the most commonly used drug design methods. The second part of the article focuses on vemurafenib. We analyze the invention of this BRAF V600E inhibitor and its analogue as well as the course of three stages of clinical trials. Then we provide information about other popular drugs for malignant melanoma, i.e. dacarbazine, ipilimumab and dabrafenib, and about the advantages of therapy with the simultaneous use of two inhibitors. Finally, we briefly discuss the role of artificial intelligence in the future of drug design.</p>","PeriodicalId":20335,"journal":{"name":"Postepy biochemii","volume":"69 3","pages":"178-187"},"PeriodicalIF":0.0,"publicationDate":"2023-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138462159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The infinite potential of a single substance: The history of tamoxifen as an example of drug repositioning 单一物质的无限潜力:他莫昔芬作为药物重新定位的一个例子的历史
Postepy biochemii Pub Date : 2023-09-03 Print Date: 2023-09-30 DOI: 10.18388/pb.2021_496
Kalina Spławska, Tomasz Wilanowski
{"title":"The infinite potential of a single substance: The history of tamoxifen as an example of drug repositioning","authors":"Kalina Spławska, Tomasz Wilanowski","doi":"10.18388/pb.2021_496","DOIUrl":"https://doi.org/10.18388/pb.2021_496","url":null,"abstract":"<p><p>Known for a long time, well-tested substances are still finding new applications in science, medicine and industry. This is a popular and cost-effective strategy because, when searching for new applications, effective methods of their large-scale production and pharmacological activity, and the results of pharmacokinetic and toxicological studies are usually already known. Tamoxifen is known mainly as a drug used in the treatment of estrogen receptor-dependent breast cancer. Despite the discovery of this effective and profitable property many years ago and the constant expansion of related applications and patents, completely new ways of using tamoxifen and its derivatives in various fields continue to appear, and the number of patents for novel applications unrelated to breast cancer remains high. The aim of this article is to illustrate drug repositioning on the example of tamoxifen and to bring the ever-developing story of discoveries related to it to a wider audience.</p>","PeriodicalId":20335,"journal":{"name":"Postepy biochemii","volume":"69 3","pages":"222-231"},"PeriodicalIF":0.0,"publicationDate":"2023-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138462160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The mTOR pathway and transgenic animals with deletion of the TSC gene in the regeneration of the nervous system and selected models of sciatic nerve damage mTOR通路和TSC基因缺失转基因动物在神经系统再生中的作用及坐骨神经损伤模型的选择
Postepy biochemii Pub Date : 2023-09-03 Print Date: 2023-09-30 DOI: 10.18388/pb.2021_489
Natalia Białoń, Krzysztof Suszyński, Mikołaj Górka, Michał Trzęsicki, Dariusz Górka, Kacper Zając, Agata Kupczak
{"title":"The mTOR pathway and transgenic animals with deletion of the TSC gene in the regeneration of the nervous system and selected models of sciatic nerve damage","authors":"Natalia Białoń, Krzysztof Suszyński, Mikołaj Górka, Michał Trzęsicki, Dariusz Górka, Kacper Zając, Agata Kupczak","doi":"10.18388/pb.2021_489","DOIUrl":"https://doi.org/10.18388/pb.2021_489","url":null,"abstract":"<p><p>Traumatic damage to the nervous system has been a common occurrence for years, reducing patients' quality of life. The mammalian target of rapamycin (mTOR) pathway plays a key role in nervous system physiology, including by controlling nerve cell survival and differentiation. Excessive activation of the mTOR pathway leads to an increase in cell cycle protein activity and apoptosis of nerve cells. Moreover, current findings suggest the involvement of the mTOR pathway in neuroplasticity. The use of transgenic animals with deletion of the TSC gene as well as various models of sciatic nerve damage, allows activation of the mTOR pathway. Currently, the results confirm that inactivation of point mutations in TSC-1 or TSC-2 genes, activates the canonical signaling pathway of the mTORC-1 complex, in turn, reactivation of the mTORC-1 pathway through the absence of the TSC-1 gene in mature neurons induces axonal regeneration. Dysfunction of the mTORC-1 pathway in Schwann cells (SC) inhibits myelination of nerve fibers. The aim of the present study is to understand the physiology and role of the mTOR pathway as well as to demonstrate the impact of TSC gene deletion in the regeneration of the nervous system. Current research on the activity of the mTOR pathway may provide new strategies to intensify peripheral nerve regeneration.</p>","PeriodicalId":20335,"journal":{"name":"Postepy biochemii","volume":"69 3","pages":"159-169"},"PeriodicalIF":0.0,"publicationDate":"2023-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138462161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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