Journal
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
Volume 40, Issue 10, Pages 4496-4506Publisher
TAYLOR & FRANCIS INC
DOI: 10.1080/07391102.2020.1858964
Keywords
α -crystallin; polyethylene glycol-400; spectroscopy; molecular modeling; Isothermal titration calorimetry; molecular docking
Categories
Funding
- Department of Science and Technology, Government of India [SR/FST/LSI-541/2012]
- Indian Council of Medical Research (ICMR) [BIC/12(16)/2014]
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This study investigated the binding of alpha-crystallin and PEG-400 using various spectroscopic techniques and molecular modeling. The results suggest a strong binding between alpha-crystallin and PEG-400, driven by van der Waals forces and hydrogen bonding. Molecular docking further confirmed the binding site of PEG-400 in alpha-crystallin.
Alpha-crystallin (alpha-crystallin) is an important eye protein having chaperone activity; its aggregation and precipitation are vital in cataract development. Polyethylene glycol-400 (PEG-400) is an important constituent of eye drops and artificial tears. The present study was targeted to study the binding of alpha-crystallin and PEG-400 employing multi spectroscopy, isothermal titration calorimetry (ITC) along with molecular modeling and docking approach. There was an apparent hypochromism in alpha-crystallin in the presence of varying PEG-400 concentrations; the binding constant obtained was 0.9 X 10(5) M-1 implying that strong binding is taking place between alpha-crystallin and PEG-400. Fluorescence spectroscopy suggested good binding of PEG-400 to alpha-crystallin with a binding constant (K) of 10(6) M-1. Moreover, fluorescence quenching studies carried out at three different temperatures suggested alpha-crystallin-PEG-400 complex formation to be guided by combination of static and dynamic modes. Thermodynamic parameters suggested alpha-crystallin-PEG-400 complex formation is driven by van der Waals forces and hydrogen bonding, making it seemingly specific. Far UV-CD spectra revealed no shift in the peak implying no alterations in the secondary structure of alpha-crystallin upon PEG-400 binding further validating complex formation. In vitro assays were further entrenched by in silico assays. Molecular modeling was used to make the functionally active form of alpha-crystallin. A binding pocket located in the beta chain was delineated by Prank Web; molecular docking showed binding of PEG-400 in this pocket. This study will give an insight into the binding of PEG-400 with alpha-crystallin and can serve as a rationale for the discovery of therapeutic molecules that can be used for the treatment of eye-related crystallin-directed diseases.
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