人类白血病细胞核质的动态变化:设计抗白血病药物的突破口

IF 2.7 4区 生物学 Q2 BIOCHEMICAL RESEARCH METHODS Journal of molecular graphics & modelling Pub Date : 2024-06-13 DOI:10.1016/j.jmgm.2024.108807
Hridoy R. Bairagya
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引用次数: 0

摘要

人类单磷酸肌苷脱氢酶(hIMPDH)是一种代谢酶,具有独特的自我组装成高阶结构的能力,可形成细胞噬菌体。hIMPDH II异构体在慢性髓性白血病(CML)癌细胞中更活跃,使其成为抗白血病治疗的一个有希望的靶点。然而,hIMPDH cytoophidia体外组装动态的结构细节和分子机制还需要更好地了解,关键是要在体外用亲细胞类聚合物重构计算核质模型,以确定其结构和功能。最后,本简短综述提出了 CML 细胞核质的计算模型及其动力学。这项关于核质的研究旨在帮助科学界了解 hIMPDH 等代谢酶如何在癌症和正常细胞中发挥作用。这项研究获得的新见解可以解释 hIMPDH 抑制剂对白血病细胞和正常细胞的结构/拓扑、几何和电子影响。它们将进一步推动核质化学反应动力学知识的发展。
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Dynamics of nucleoplasm in human leukemia cells: A thrust towards designing anti-leukemic agents

The human inosine monophosphate dehydrogenase (hIMPDH) is a metabolic enzyme that possesses a unique ability to self-assemble into higher-order structures, forming cytoophidia. The hIMPDH II isoform is more active in chronic myeloid leukemia (CML) cancer cells, making it a promising target for anti-leukemic therapy. However, the structural details and molecular mechanisms of the dynamics of hIMPDHcytoophidia assembly in vitro need to be better understood, and it is crucial to reconstitute the computational nucleoplasm model with cytophilic-like polymers in vitro to characterize their structure and function. Finally, a computational model and its dynamics of the nucleoplasm for CML cells have been proposed in this short review. This research on nucleoplasm aims to aid the scientific community's understanding of how metabolic enzymes like hIMPDH function in cancer and normal cells.

However, validating and justifying the computational results from modeling and simulation with experimental data is essential. The new insights gained from this research could explain the structure/topology, geometrical, and electronic consequences of hIMPDH inhibitors on leukemic and normal cells. They could lead to further advancements in the knowledge of nucleoplasmic chemical reaction dynamics.

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来源期刊
Journal of molecular graphics & modelling
Journal of molecular graphics & modelling 生物-计算机:跨学科应用
CiteScore
5.50
自引率
6.90%
发文量
216
审稿时长
35 days
期刊介绍: The Journal of Molecular Graphics and Modelling is devoted to the publication of papers on the uses of computers in theoretical investigations of molecular structure, function, interaction, and design. The scope of the journal includes all aspects of molecular modeling and computational chemistry, including, for instance, the study of molecular shape and properties, molecular simulations, protein and polymer engineering, drug design, materials design, structure-activity and structure-property relationships, database mining, and compound library design. As a primary research journal, JMGM seeks to bring new knowledge to the attention of our readers. As such, submissions to the journal need to not only report results, but must draw conclusions and explore implications of the work presented. Authors are strongly encouraged to bear this in mind when preparing manuscripts. Routine applications of standard modelling approaches, providing only very limited new scientific insight, will not meet our criteria for publication. Reproducibility of reported calculations is an important issue. Wherever possible, we urge authors to enhance their papers with Supplementary Data, for example, in QSAR studies machine-readable versions of molecular datasets or in the development of new force-field parameters versions of the topology and force field parameter files. Routine applications of existing methods that do not lead to genuinely new insight will not be considered.
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