Molecular interactions of the anticancer agent ellipticine with glycosaminoglycans by in silico analysis

Ferenc Zsila , Sergey Samsonov


The anticancer agent ellipticine (ELP) functions as a DNA intercalating drug. Depending on the pH of the medium, it exists both in a neutral and a protonated form. In acidic extracellular microenvironment characteristic to malignant tissues, charged ELP molecules can also bind to glycosaminoglycans (GAGs), linear anionic periodic polysaccharides, which interact with various protein targets affecting diverse cellular events. Although a previous experimental work indicated specific GAG binding of protonated ELP, the underlying molecular mechanisms remain to be elucidated. From a computational point of view, analysis of molecular systems containing GAGs is challenging due to their high flexibility, variability in sulfation patterns and a key role of electrostatics and solvent-mediated interactions. In the present study, molecular dynamics-based approaches were employed to model ELP-GAG interactions in order to unveil the atomistic details of this biologically relevant molecular system. We characterized dynamic and energetic properties of three kinds of ELP-GAG complexes to rationalize and complement the available experimental data. The results reported herein provide insight into possible molecular pathways by which biological actions of ELP are mediated.
Author Ferenc Zsila - [Magyar Tudomanyos Akademia]
Ferenc Zsila,,
, Sergey Samsonov (FCh / DTCh / LMM)
Sergey Samsonov,,
- Laboratory of Molecular Modeling
Journal seriesCarbohydrate Research, ISSN 0008-6215, (A 25 pkt)
Issue year2018
Publication size in sheets0.5
Keywords in Englishglycosaminoglycans, ellipticine, molecular dynamics, protonation state
ASJC Classification2700 General Medicine; 1303 Biochemistry; 1602 Analytical Chemistry; 1605 Organic Chemistry
Languageen angielski
LicenseRepository; author's final; Uznanie Autorstwa - Na Tych Samych Warunkach (CC-BY-SA); with publication
Zsila_Ferenc_Molecular_interactions_of_the_anticancer_agent_ellipticine_with_glycosaminoglycans_by_in_silico_analysis_2018.pdf 208.81 KB
Score (nominal)25
Score sourcejournalList
ScoreMinisterial score = 25.0, 29-05-2020, ArticleFromJournal
Publication indicators WoS Citations = 1; Scopus Citations = 2; Scopus SNIP (Source Normalised Impact per Paper): 2018 = 0.731; WoS Impact Factor: 2018 = 1.873 (2) - 2018=1.908 (5)
Citation count*2 (2020-05-30)
Additional fields
LicencjaUtwór jest udostępniany na licencji Creative Commons Uznanie autorstwa-Na tych samych warunkach 4.0 Międzynarodowe (CC BY-SA 4.0)
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* presented citation count is obtained through Internet information analysis and it is close to the number calculated by the Publish or Perish system.
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