Comprehensive and quantitative molecular docking analysis of rhodopsin-retinal interactions

Area of Science:

• Biochemistry
• Structural Biology
• Vision Science

Background:

• Rhodopsin, a G-protein coupled receptor, is crucial for vertebrate vision.
• Numerous rhodopsin structures in different conformational states are available, enabling large-scale interaction analysis.
• Understanding retinal binding dynamics is key to elucidating rhodopsin activation.

Purpose of the Study:

• To quantitatively analyze retinal binding affinities across diverse rhodopsin conformational states.
• To compare the binding of 11-cis-retinal and all-trans-retinal to various rhodopsin structures.
• To investigate how protein binding partners and mutations affect retinal-rhodopsin interactions.

Main Methods:

• Database creation of 66 bovine rhodopsin structures from the Protein Data Bank.
• Classification of structures into dark-state, opsin, meta-rhodopsin II, and photo-intermediate states.
• Computational analysis using DiffDock and GNINA for minimized affinity calculations.

Main Results:

• Meta-rhodopsin II structures preferentially bind all-trans-retinal; dark-state structures bind 11-cis-retinal.
• Photo-intermediate states (lumi- and batho-rhodopsin) show enhanced binding affinity for both retinal isomers due to pocket flexibility.
• Retinal binding affinity decreases in opsin and active states bound to proteins.

Conclusions:

• Rhodopsin's binding pocket flexibility significantly influences retinal affinity across different conformational states.
• The study provides quantitative data on retinal-rhodopsin interactions, advancing our understanding of the visual cycle.
• Novel insights into the rhodopsin activation mechanism are offered through large-scale structural and computational analysis.