Photoproducts of bacteriorhodopsin mutants: a molecular dynamics study

Area of Science:

• Biophysics
• Computational Biology
• Structural Biology

Background:

• Bacteriorhodopsin (bR) is a light-driven proton pump crucial for cellular energy generation.
• Understanding the photoproducts of bR is key to elucidating its pumping mechanism.
• Specific mutations in bR can alter its photochemical properties and function.

Purpose of the Study:

• To investigate the photoproducts formed by wild-type bacteriorhodopsin (bR) and its mutants (D85N, D85T, D212N, Y57F).
• To correlate the types of photoproducts with the proton pumping efficiency of bR variants.
• To explain the observed functional differences in bR mutants using molecular dynamics simulations.

Main Methods:

• Utilized molecular dynamics (MD) simulations to model the photoisomerization and relaxation processes in bR.
• Performed 50 independent MD simulations for each protein variant (wild-type and mutants).
• Classified the resulting photoproducts into four distinct categories based on retinal configuration and protonation states.

Main Results:

• Wild-type bR and the Y57F mutant predominantly formed class 1 (13-cis retinal, N-H+ toward Asp-96) and class 2 (13-cis retinal, N-H+ toward Asp-85) photoproducts.
• Mutants D85N, D85T, and D212N almost exclusively generated class 1 photoproducts.
• Class 2 photoproducts are suggested to be essential for initiating the functional proton pump cycle.

Conclusions:

• The predominance of class 1 photoproducts in D85N, D85T, and D212N mutants correlates with the reversal of proton pumping.
• These findings support the hypothesis that only specific photoproducts (class 2) are functionally active in the bR proton pump cycle.
• The study provides a molecular basis for understanding the altered photochemistry and function of bR mutants.