Insight into the binding of PEG-400 with eye protein alpha-crystallin: Multi spectroscopic and computational approach: possible therapeutics targeting eye diseases.

Anas Shamsi, Taj Mohammad, Saleha Anwar, Khalida Nasreen, Md Imtaiyaz Hassan, Faizan Ahmad, Asimul Islam

Journal of biomolecular structure & dynamics 2022 Jul

filter terms:

Alpha-crystallin (α-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 α-crystallin and PEG-400 employing multi spectroscopy, isothermal titration calorimetry (ITC) along with molecular modeling and docking approach. There was an apparent hypochromism in α-crystallin in the presence of varying PEG-400 concentrations; the binding constant obtained was 0.9 X 105 M-1 implying that strong binding is taking place between α-crystallin and PEG-400. Fluorescence spectroscopy suggested good binding of PEG-400 to α-crystallin with a binding constant (K) of 106 M-1. Moreover, fluorescence quenching studies carried out at three different temperatures suggested α-crystallin-PEG-400 complex formation to be guided by combination of static and dynamic modes. Thermodynamic parameters suggested α-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 α-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 α-crystallin. A binding pocket located in the β 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 α-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. HighlightsPEG-400 is a constituent of lubricant eye drops.Molecular modelling gave functionally active crystallin.Molecular docking showed PEG-400 in the binding pocket.Fluorescence binding revealed good bindingα-crystallin and PEG400.The α-crystallin-PEG-400 complex was guided by static and dynamic quenching.Communicated by Ramaswamy H. Sarma.

Citation

Anas Shamsi, Taj Mohammad, Saleha Anwar, Khalida Nasreen, Md Imtaiyaz Hassan, Faizan Ahmad, Asimul Islam. Insight into the binding of PEG-400 with eye protein alpha-crystallin: Multi spectroscopic and computational approach: possible therapeutics targeting eye diseases. Journal of biomolecular structure & dynamics. 2022 Jul;40(10):4496-4506