Deciphering druggability potential of some proteins of Candida albicans biofilm using subtractive proteomics approach

IF 2.1 4区 综合性期刊 Q2 MULTIDISCIPLINARY SCIENCES
Dushyant Kumar, Awanish Kumar
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Abstract

Candida albicans is an opportunistic fungal pathogen that lives as a commensal microorganism that transforms into a pathogenic form and builds a protective community called biofilms upon getting favorable conditions. The narrow range and debilitated efficiency of drug arsenals against the limited druggable target of C. albicans attracted the attention of researchers around the globe. From the proteomic database of C. albicans, 261 proteins playing functional roles during biofilm development were scrutinized through a literature survey. Upon further scrutiny, the proteins were first checked for non-homology with human proteome. After the establishment of non-homology, the protein's essentiality was established by constructing a protein–protein interaction network. Essentiality was found with two different confidence scores [High (0.7) and Highest (0.9)], and 45 and 15 proteins were selected, respectively. The highest confidence scorer 15 proteins were 3D modeled, and ligand binding grooves were predicted after structural validation. Lastly, the half-life of these 15 essential proteins was deduced, and expression levels during biofilm development were measured through a literature survey and web databases. Through the in-silico application, we established the 15 proteins as new druggable targets. The result of the study could further indicate the design of some effective antifungal drug candidates. However, these potential druggable targets need to be extended in vitro experiments and validation.

Abstract Image

利用减法蛋白质组学方法破译白色念珠菌生物膜某些蛋白质的可药性潜力
白色念珠菌是一种机会性真菌病原体,它以共生微生物的形式存在,一旦获得有利条件,就会转变为致病形式,并建立一个称为生物膜的保护性群落。针对白僵菌有限的可药用靶点,药物武库的范围狭窄且效率低下,这引起了全球研究人员的关注。通过文献调查,研究人员从白僵菌蛋白质组数据库中筛选出 261 个在生物膜形成过程中发挥功能作用的蛋白质。在进一步研究中,首先检查了这些蛋白质与人类蛋白质组是否存在同源性。在确定非同源性后,通过构建蛋白质-蛋白质相互作用网络来确定蛋白质的本质。根据两种不同的置信度得分[高(0.7)和最高(0.9)],分别选出了 45 个和 15 个蛋白质。对置信度得分最高的 15 个蛋白质进行了三维建模,并在结构验证后预测了配体结合沟。最后,通过文献调查和网络数据库,推断出这 15 种重要蛋白质的半衰期,并测定了它们在生物膜发育过程中的表达水平。通过这项研究,我们将这 15 个蛋白质确定为新的药物靶点。研究结果可进一步指明一些有效抗真菌候选药物的设计方向。不过,这些潜在的可药用靶点还需要进一步的体外实验和验证。
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来源期刊
Rendiconti Lincei-Scienze Fisiche E Naturali
Rendiconti Lincei-Scienze Fisiche E Naturali MULTIDISCIPLINARY SCIENCES-
CiteScore
4.10
自引率
10.00%
发文量
70
审稿时长
>12 weeks
期刊介绍: Rendiconti is the interdisciplinary scientific journal of the Accademia dei Lincei, the Italian National Academy, situated in Rome, which publishes original articles in the fi elds of geosciences, envi ronmental sciences, and biological and biomedi cal sciences. Particular interest is accorded to papers dealing with modern trends in the natural sciences, with interdisciplinary relationships and with the roots and historical development of these disciplines.
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