Georgios Mikaelian, Grigorios Megariotis* and Doros N. Theodorou,
{"title":"新型蒽环类药物与寡核苷酸 DNA 和环糊精在水环境中的相互作用","authors":"Georgios Mikaelian, Grigorios Megariotis* and Doros N. Theodorou, ","doi":"10.1021/acs.jpcb.4c02213","DOIUrl":null,"url":null,"abstract":"<p >Berubicin, a chemotherapy medication belonging to the class of anthracyclines, is simulated in double-stranded DNA sequences and cyclodextrins in an aqueous environment via full-atom molecular dynamics simulations on the time scale of microseconds. The drug is studied in both the neutral and protonated states so as to better comprehend the role of its charge in the formed complexes. The noncovalent berubicin–DNA and berubicin–cyclodextrin complexes are investigated in detail, paying special attention to their thermodynamic description by employing the double decoupling method, the solvent balance method, the weighted solvent accessible surface model, and the linear interaction energy method. A novel approach for extracting the desolvation thermodynamics of the binding process is also presented. Both the binding and desolvation Gibbs energies are decomposed into entropic and enthalpic contributions so as to elucidate the nature of complexation and its driving forces. Selected structural and geometrical properties of all the complexes, which are all stable, are analyzed. Both cyclodextrins under consideration are widely utilized for drug delivery purposes, and a comparative investigation between their bound states with berubicin is carried out.</p>","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":null,"pages":null},"PeriodicalIF":2.8000,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acs.jpcb.4c02213","citationCount":"0","resultStr":"{\"title\":\"Interactions of a Novel Anthracycline with Oligonucleotide DNA and Cyclodextrins in an Aqueous Environment\",\"authors\":\"Georgios Mikaelian, Grigorios Megariotis* and Doros N. Theodorou, \",\"doi\":\"10.1021/acs.jpcb.4c02213\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p >Berubicin, a chemotherapy medication belonging to the class of anthracyclines, is simulated in double-stranded DNA sequences and cyclodextrins in an aqueous environment via full-atom molecular dynamics simulations on the time scale of microseconds. The drug is studied in both the neutral and protonated states so as to better comprehend the role of its charge in the formed complexes. The noncovalent berubicin–DNA and berubicin–cyclodextrin complexes are investigated in detail, paying special attention to their thermodynamic description by employing the double decoupling method, the solvent balance method, the weighted solvent accessible surface model, and the linear interaction energy method. A novel approach for extracting the desolvation thermodynamics of the binding process is also presented. Both the binding and desolvation Gibbs energies are decomposed into entropic and enthalpic contributions so as to elucidate the nature of complexation and its driving forces. Selected structural and geometrical properties of all the complexes, which are all stable, are analyzed. Both cyclodextrins under consideration are widely utilized for drug delivery purposes, and a comparative investigation between their bound states with berubicin is carried out.</p>\",\"PeriodicalId\":60,\"journal\":{\"name\":\"The Journal of Physical Chemistry B\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.8000,\"publicationDate\":\"2024-06-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://pubs.acs.org/doi/epdf/10.1021/acs.jpcb.4c02213\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"The Journal of Physical Chemistry B\",\"FirstCategoryId\":\"1\",\"ListUrlMain\":\"https://pubs.acs.org/doi/10.1021/acs.jpcb.4c02213\",\"RegionNum\":2,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"CHEMISTRY, PHYSICAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"The Journal of Physical Chemistry B","FirstCategoryId":"1","ListUrlMain":"https://pubs.acs.org/doi/10.1021/acs.jpcb.4c02213","RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CHEMISTRY, PHYSICAL","Score":null,"Total":0}
引用次数: 0
摘要
通过全原子分子动力学模拟,在微秒级的时间尺度上模拟了水环境中双链 DNA 序列和环糊精中的贝鲁霉素(一种属于蒽环类的化疗药物)。研究了药物的中性和质子化状态,以便更好地理解其电荷在形成的复合物中的作用。详细研究了贝鲁霉素-DNA 和贝鲁霉素-环糊精的非共价复合物,特别关注其热力学描述,采用了双解耦法、溶剂平衡法、加权溶剂可及表面模型和线性相互作用能法。此外,还介绍了一种提取结合过程中脱溶热力学的新方法。结合和解溶解吉布斯能被分解为熵贡献和焓贡献,从而阐明了络合的性质及其驱动力。分析了所有络合物的部分结构和几何特性,这些络合物都很稳定。所研究的两种环糊精都被广泛用于给药目的,本文对它们与贝鲁霉素的结合态进行了比较研究。
Interactions of a Novel Anthracycline with Oligonucleotide DNA and Cyclodextrins in an Aqueous Environment
Berubicin, a chemotherapy medication belonging to the class of anthracyclines, is simulated in double-stranded DNA sequences and cyclodextrins in an aqueous environment via full-atom molecular dynamics simulations on the time scale of microseconds. The drug is studied in both the neutral and protonated states so as to better comprehend the role of its charge in the formed complexes. The noncovalent berubicin–DNA and berubicin–cyclodextrin complexes are investigated in detail, paying special attention to their thermodynamic description by employing the double decoupling method, the solvent balance method, the weighted solvent accessible surface model, and the linear interaction energy method. A novel approach for extracting the desolvation thermodynamics of the binding process is also presented. Both the binding and desolvation Gibbs energies are decomposed into entropic and enthalpic contributions so as to elucidate the nature of complexation and its driving forces. Selected structural and geometrical properties of all the complexes, which are all stable, are analyzed. Both cyclodextrins under consideration are widely utilized for drug delivery purposes, and a comparative investigation between their bound states with berubicin is carried out.
期刊介绍:
An essential criterion for acceptance of research articles in the journal is that they provide new physical insight. Please refer to the New Physical Insights virtual issue on what constitutes new physical insight. Manuscripts that are essentially reporting data or applications of data are, in general, not suitable for publication in JPC B.