Dynamic Comparison of Binding Pocket of Berberine Protein Crystals

IF 1.2 4区 医学 Q4 CHEMISTRY, MEDICINAL
Jin-Rong Ma, Qiu-Rong Huang, Ruo-Jun Man, Lin-Guo Zhao, Dong-Dong Li
{"title":"Dynamic Comparison of Binding Pocket of Berberine Protein Crystals","authors":"Jin-Rong Ma, Qiu-Rong Huang, Ruo-Jun Man, Lin-Guo Zhao, Dong-Dong Li","doi":"10.2174/0115701808291656240722095841","DOIUrl":null,"url":null,"abstract":"Introduction: Berberine is an important isoquinoline alkaloid that has various pharmacological properties. The comparison of the binding pocket similarity of berberine is regarded as the starting point for deciphering various activities. Eight berberine protein crystals were clustered and studied by molecular dynamics (MD) simulations to investigate common features of berberine binding pockets. Method: Root Mean Square Deviation (RMSD) results showed that berberine was able to bind to each protein in a stable manner. Residue analysis showed that the stability of residue composition of different protein pockets varied. This is also consistent with the results of the pocket similarity analysis: PS-score curves of most proteins fluctuated to varying degrees. The binding pocket of 3BTI in homogeneous protein analysis exhibited high stability (PS-scoremean = 0.703 and PS-scoremin = 0.5664). Pocket similarity analysis between two heterologous proteins showed that most of PS-score values were in the interval of 0.3-0.35, and PS-score values of 3D6Y were relatively high when compared with the other three proteins. Results: Pocket residue matching analysis showed that GLU145/VAL147/ILE182/TYR229/GLU253 in 3D6Y can be matched structurally to the corresponding residues in 1JUM, 2QVD, and 5Y0V, respectively, which can be considered as an important pocket feature for the berberine binding. Nevertheless, the obtained matched residues are limited to the category of pocket structural similarity. Conclusion: This was the first study in which dynamic comparison of berberine binding pockets were used to discover pocket patterns. These results were of great significance for the polypharmacological study, the identification of potential off-targets, and the repurposing of berberine. conclusion: This was the first study in which dynamic comparisons of berberine binding pockets were used to discover interaction patterns. These results were of great significance for the polypharmacological study, the identification of potential off-targets, and the repurposing of berberine.","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":null,"pages":null},"PeriodicalIF":1.2000,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Letters in Drug Design & Discovery","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2174/0115701808291656240722095841","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
引用次数: 0

Abstract

Introduction: Berberine is an important isoquinoline alkaloid that has various pharmacological properties. The comparison of the binding pocket similarity of berberine is regarded as the starting point for deciphering various activities. Eight berberine protein crystals were clustered and studied by molecular dynamics (MD) simulations to investigate common features of berberine binding pockets. Method: Root Mean Square Deviation (RMSD) results showed that berberine was able to bind to each protein in a stable manner. Residue analysis showed that the stability of residue composition of different protein pockets varied. This is also consistent with the results of the pocket similarity analysis: PS-score curves of most proteins fluctuated to varying degrees. The binding pocket of 3BTI in homogeneous protein analysis exhibited high stability (PS-scoremean = 0.703 and PS-scoremin = 0.5664). Pocket similarity analysis between two heterologous proteins showed that most of PS-score values were in the interval of 0.3-0.35, and PS-score values of 3D6Y were relatively high when compared with the other three proteins. Results: Pocket residue matching analysis showed that GLU145/VAL147/ILE182/TYR229/GLU253 in 3D6Y can be matched structurally to the corresponding residues in 1JUM, 2QVD, and 5Y0V, respectively, which can be considered as an important pocket feature for the berberine binding. Nevertheless, the obtained matched residues are limited to the category of pocket structural similarity. Conclusion: This was the first study in which dynamic comparison of berberine binding pockets were used to discover pocket patterns. These results were of great significance for the polypharmacological study, the identification of potential off-targets, and the repurposing of berberine. conclusion: This was the first study in which dynamic comparisons of berberine binding pockets were used to discover interaction patterns. These results were of great significance for the polypharmacological study, the identification of potential off-targets, and the repurposing of berberine.
小檗碱蛋白晶体结合口袋的动态比较
简介小檗碱是一种重要的异喹啉生物碱,具有多种药理特性。比较小檗碱结合口袋的相似性被认为是解读其各种活性的起点。通过分子动力学(MD)模拟对八种小檗碱蛋白晶体进行聚类研究,以探讨小檗碱结合口袋的共同特征。研究方法均方根偏差(RMSD)结果显示,小檗碱能够以稳定的方式与每种蛋白质结合。残基分析表明,不同蛋白质口袋中残基组成的稳定性各不相同。这也与口袋相似性分析的结果一致:大多数蛋白质的 PS 评分曲线都有不同程度的波动。在同源蛋白质分析中,3BTI 的结合口袋表现出较高的稳定性(PS-scoremean = 0.703 和 PS-scoremin = 0.5664)。两个异源蛋白之间的口袋相似性分析表明,大多数 PS-score 值在 0.3-0.35 之间,与其他三个蛋白相比,3D6Y 的 PS-score 值相对较高。结果口袋残基匹配分析表明,3D6Y中的GLU145/VAL147/ILE182/TYR229/GLU253可分别与1JUM、2QVD和5Y0V中的相应残基进行结构匹配,这可被视为小檗碱结合的一个重要口袋特征。然而,所获得的匹配残基仅限于口袋结构相似性类别。结论这是首次利用动态比较小檗碱结合口袋来发现口袋模式的研究。这些结果对小檗碱的多药理研究、潜在非靶点的识别和再利用具有重要意义:这是首次利用动态比较小檗碱结合口袋来发现相互作用模式的研究。这些结果对于小檗碱的多药理研究、潜在非靶点的识别和再利用具有重要意义。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
CiteScore
1.80
自引率
10.00%
发文量
245
审稿时长
3 months
期刊介绍: Aims & Scope Letters in Drug Design & Discovery publishes letters, mini-reviews, highlights and guest edited thematic issues in all areas of rational drug design and discovery including medicinal chemistry, in-silico drug design, combinatorial chemistry, high-throughput screening, drug targets, and structure-activity relationships. The emphasis is on publishing quality papers very rapidly by taking full advantage of latest Internet technology for both submission and review of manuscripts. The online journal is an essential reading to all pharmaceutical scientists involved in research in drug design and discovery.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信